PrEP Use, Sexual Behaviour, and PrEP Adherence Among Men who have Sex with Men Living in Wales Prior to and During the COVID-19 Pandemic.

We examined PrEP use, condomless anal sex (CAS), and PrEP adherence among men who have sex with men (MSM) attending sexual health clinics in Wales, UK. In addition, we explored the association between the introduction of measures to control transmission of SARS-CoV-2 on these outcomes. We conducted an ecological momentary assessment study of individuals in receipt of PrEP in Wales. Participants used an electronic medication cap to record PrEP use and completed weekly sexual behaviour surveys. We defined adherence to daily PrEP as the percentage of CAS episodes covered by daily PrEP (preceded by ≥ 3 days of PrEP and followed by ≥ 2 days). Sixty participants were recruited between September 2019 and January 2020. PrEP use data prior to the introduction of control measures were available over 5785 person-days (88%) and following their introduction 7537 person-days (80%). Data on CAS episodes were available for 5559 (85%) and 7354 (78%) person-days prior to and following control measures respectively. Prior to the introduction of control measures, PrEP was taken on 3791/5785 (66%) days, there were CAS episodes on 506/5559 (9%) days, and 207/406 (51%) of CAS episodes were covered by an adequate amount of daily PrEP. The introduction of pandemic-related control measures was associated with a reduction in PrEP use (OR 0.44, 95%CI 0.20-0.95), CAS (OR 0.35, 95%CI 0.17-0.69), and PrEP adherence (RR = 0.55, 95%CI 0.34-0.89) and this may have implications for the health and wellbeing of PrEP users and, in addition to disruption across sexual health services, may contribute to wider threats across the HIV prevention cascade.

Improved sexual history taking in the 2012 BASHH asymptomatic screening re-audit.

Effective asymptomatic screening for sexually transmitted infections is an important public health service because a significant proportion of sexually transmitted infections do not present with symptoms. In 2009, the National Audit Group of the British Association of Sexual Health and HIV (BASHH) audited the management of asymptomatic patients and recommended increased documentation about oral and anal sex, regional strategies for nucleic acid amplification test (NAAT) use for gonorrhoea, improved screening for hepatitis B in men who have sex with men and an increase in screening for HIV. The 2012 audit used web-based forms to collect submissions from 180 consultant-led centres (65% response rate) that included episodes of care from 6669 asymptomatic patients. An improvement was demonstrated for all the areas measured during the 2009 audit. A doubling of gonorrhoea testing using NAATs was seen and yet 10% of asymptomatic patients continued to have microscopy despite these tests not being recommended by BASHH guidelines. This audit recommends universal adoption of gonorrhoea NAATs across the United Kingdom.

Effective use of an audit tool devised to optimize the management of syphilis in an integrated sexual health clinic.

The objective of this study was to audit the management of syphilis in our integrated sexual health clinic according to the British Association for Sexual Health and HIV (BASHH) guideline using the 'Treponemal Infection Care' (TIC) audit tool devised by our clinic. The case notes of patients diagnosed with all stages of syphilis during an 18-month period were reviewed. At the time of diagnosis, the departmental TIC proforma was filled in: this proforma details BASHH auditable outcomes. The case notes of 83 patients diagnosed with syphilis during the audit period were reviewed. The majority of patients were men (76), men who had sex with men (69), HIV-negative (59) and were British (68). In line with current guidance all patients had a baseline Venereal Disease Research Laboratory (VDRL) titre at the start of treatment (target: 100%) and 97% of diagnosed patients completed treatment (target: 95%). A 'response to treatment' according to the decrease in VDRL was demonstrated in 50 (60%) patients with two (2%) patients failing to respond according to these criteria. However, 19 (23%) patients failed to return for their VDRL tests before demonstrating an adequate response to treatment, despite repeated attempts to contact them by letter and telephone. Fifty-four patients had at least 50% of their partners documented as traceable. Of those who were contactable, 100% attended for screening or treatment (target: 60%). In conclusion, our department performed well against BASHH auditable outcome targets. The introduction of the TIC proforma greatly facilitated the ease of audit and is a valuable tool within our clinic setting, which may have positively influenced our audit outcomes. Further action is required to highlight the importance of follow-up VDRLs to patients.

Audit of a network of sexually transmitted infections centred in South Wales.

The aim of this article is to audit the distribution and frequency of sexually transmitted infections (STIs) within a sexual network centred in South Wales. After diagnosis of a new case of HIV in February 2007, partner notification, HIV and STI testing were undertaken. Those traced were given information regarding safe sex practices and informed they had been in contact with HIV. Genitourinary (GU) medicine case-notes of contacts identified in the network were reviewed from February 2007 to 1 July 2008. Frequency and distribution of new diagnoses of STIs made on original identification in the network in 2007 were compared with subsequent new diagnoses within the network. One hundred and eighteen men who have sex with men (MSMs) and five women were identified in the original network in 2007. By 1 July 2008, 65 new sexual contacts (all MSMs) were added to the network and there were 25 new STI diagnoses in 13 contacts. Seven contacts originally identified in the cluster in 2007 were diagnosed with 16 of the new STIs. In conclusion, the sexual network has evolved by increasing in size with multiple new STIs diagnosed. The highest risk of STIs occurred in relatively few individuals. Standard interventions in health promotion in the GU medicine setting were not universally successful in preventing high-risk behaviour.

Investigation of an HIV transmission cluster centred in South Wales.

OBJECTIVE: To describe an HIV transmission cluster centred in South Wales by the analysis of partner notification outcomes and demographic characteristics of individuals identified in the sexual network. METHODS: After diagnosis of the index case, HIV testing and partner notification were undertaken by Cardiff Genitourinary Medicine Clinic in collaboration with the local Health Protection Team, National Public Health Service for Wales and Terrence Higgins Trust Cymru. Rapid test and standard venepuncture methods were used for HIV screening and the resulting clinical and behavioural data were analysed. RESULTS: Of the 123 individuals identified in the sexual network, all were men who had sex with men (MSM) except for seven men who self-identified as bisexual and five heterosexual women. Fifteen new cases of HIV were diagnosed; all were men. Partner notification outcomes are as follows: 104 provider referrals were made, 57 were successfully contacted with known outcomes, 14 were successfully contacted but with unknown outcomes and 33 were uncontactable. Fifteen patient referrals were made, 11 had known outcomes but four had unknown outcomes. Four patients self-referred. Eleven reported previous HIV diagnosis. The sexual network was distributed over South and West Wales extending into England, with high reported rates of unprotected anal intercourse, previous HIV tests and concurrent sexually transmitted infections. A one in four positive rate for those with a known HIV status outcome and a 68% provider referral success rate compares favourably with other studies. CONCLUSIONS: Partner notification revealed a relatively young, well-educated HIV network with high-risk behaviour and ongoing transmission despite previous knowledge and awareness of HIV. This analysis adds to the evidence supporting HIV partner notification in MSM.

Complete genomic sequence of the human ABCA1 gene: analysis of the human and mouse ATP-binding cassette A promoter.

The ABCA1 gene, a member of the ATP-binding cassette A (ABCA1) transporter superfamily, encodes a membrane protein that facilitates the cellular efflux of cholesterol and phospholipids. Mutations in ABCA1 lead to familial high density lipoprotein deficiency and Tangier disease. We report the complete human ABCA1 gene sequence, including 1,453 bp of the promoter, 146,581 bp of introns and exons, and 1 kb of the 3' flanking region. The ABCA1 gene spans 149 kb and comprises 50 exons. Sixty-two repetitive Alu sequences were identified in introns 1-49. The transcription start site is 315 bp upstream of a newly identified initiation methionine codon and encodes an ORF of 6,783 bp. Thus, the ABCA1 protein is comprised of 2,261 aa. Analysis of the 1,453 bp 5' upstream of the transcriptional start site reveals multiple binding sites for transcription factors with roles in lipid metabolism. Comparative analysis of the mouse and human ABCA1 promoter sequences identified specific regulatory elements, which are evolutionarily conserved. The human ABCA1 promoter fragment -200 to -80 bp that contains binding motifs for SP1, SP3, E-box, and AP1 modulates cellular cholesterol and cAMP regulation of ABCA1 gene expression. These combined findings provide insights into ABCA1-mediated regulation of cellular cholesterol metabolism and will facilitate the identification of new pharmacologic agents for the treatment of atherosclerosis in humans.

Does PBL Matter? Relations Between Instructional Context, Learning Strategies, and Learning Outcomes.

Purpose: To compare learning strategies used in Problem based learning (PBL) and lectures, and the relations between learning strategies and learning outcomes to determine how different learning strategies associated with PBL and lectures contribute to aspects of clinical competence. Design: The 52-item learning strategies questionnaire was given to preclinical medical students during lecture and PBL sessions in first and third year from 1994 to 1998. Response patterns were compared across the two contexts and factor structures investigated. Regression analyses examined relations between learning strategies and outcomes. Main Outcome Measures/Results: Comparison of responses on the 326 complete pairs of lecture and PBL questionnaires indicated differences at the 0.05 level on 44 of the 52 items. The mean differences were greater than 0.5 (on a 5 point scale) at the 0.001 level for 20 items. Of these, five strategies were used more often in PBL and 15 in lectures. Comparisons of learning strategy use across years showed significant changes with time in both instructional contexts. Principal component analysis revealed a stable factor structure with 4 factors distinctly associated with PBL and 4 factors with the lecture learning context. The remaining 6 factors were mixed and independent of context. Exploratory regression analysis revealed that learning outcomes in examinations were influenced by learning strategies. Multiple choice performance was positively predicted by learning associated with lecture class notes and negatively by group work, whereas the OSCE (objective structured clinical exam) performance was positively predicted by class participation in PBL, self-directed note making and lecture class notes. Conclusion: We have developed a learning strategies questionnaire that shows that students' learning strategies are influenced by instructional context, and patterns of learning strategy use change over time. There is tentative evidence that the students' learning strategies influence learning outcomes.

Human ATP-binding cassette transporter 1 (ABC1): genomic organization and identification of the genetic defect in the original Tangier disease kindred.

Tangier disease is characterized by low serum high density lipoproteins and a biochemical defect in the cellular efflux of lipids to high density lipoproteins. ABC1, a member of the ATP-binding cassette family, recently has been identified as the defective gene in Tangier disease. We report here the organization of the human ABC1 gene and the identification of a mutation in the ABC1 gene from the original Tangier disease kindred. The organization of the human ABC1 gene is similar to that of the mouse ABC1 gene and other related ABC genes. The ABC1 gene contains 49 exons that range in size from 33 to 249 bp and is over 70 kb in length. Sequence analysis of the ABC1 gene revealed that the proband for Tangier disease was homozygous for a deletion of nucleotides 3283 and 3284 (TC) in exon 22. The deletion results in a frameshift mutation and a premature stop codon starting at nucleotide 3375. The product is predicted to encode a nonfunctional protein of 1,084 aa, which is approximately half the size of the full-length ABC1 protein. The loss of a Mnl1 restriction site, which results from the deletion, was used to establish the genotype of the rest of the kindred. In summary, we report on the genomic organization of the human ABC1 gene and identify a frameshift mutation in the ABC1 gene of the index case of Tangier disease. These results will be useful in the future characterization of the structure and function of the ABC1 gene and the analysis of additional ABC1 mutations in patients with Tangier disease.

Adenovirus-mediated expression of hepatic lipase in LCAT transgenic mice.

In order to evaluate the coordinate role that hepatic lipase (HL) and lecithin:cholesterol acyltransferase (LCAT) play in modulating HDL particle heterogeneity and function in vivo we utilized recombinant adenovirus to express HL in control and LCAT transgenic mice. Adenovirus-mediated expression of human HL in control (n = 4, LCAT activity = 42 +/- 1 nmol/ml per h) and LCAT-tg mice (n = 4, LCAT activity = 3566 +/- 93 nmol/ml per h) resulted in post heparin HL activities of 24,358 +/- 6080 and 27,266 +/- 7985 nmol/ml per min, respectively. Overexpression of HL led to significant reductions in total cholesterol, phospholipids, and HDL cholesterol in both LCAT-tg (62, 62, and 63%, P < 0.05) and control mice (68, 63, and 78%, P < 0.01) as well as to the formation of more homogenous HDL. However, compared to control animals, the reductions in the plasma concentrations of HDL-cholesterol and apoA-I were less in LCAT-tg mice (HDL-cholesterol: -62 +/- 15% vs. -78 +/- 15%, P = 0.18; apoA-I: -36 +/- 7% vs. -76 +/- 8%, P < 0.0005). Gel filtration analysis revealed that in LCAT-tg mice the apoE-rich HDL1 was preferentially reduced by expression of HL in vivo. Compared to control mice the reduction in the apoA-I/A-II HDL in transgenic mice was significantly less indicating that a subset of HDL in LCAT transgenic mice are resistant to the action of HL. These combined data support a role for both HL and LCAT in modulating HDL heterogeneity and function, properties which may ultimately affect the ability of LCAT transgenic mouse HDL to function in the process of reverse cholesterol transport.