Rapid aminations of functionalized aryl fluorosulfates in water.

Aryl fluorosulfates of varying complexities have been used in amination reactions in water using a new Pd oxidative addition complex (OAC-1) developed specifically to match the needs of the fine chemicals industry, not only in terms of functional group tolerance, but also reflecting time considerations associated with these important C-N couplings. Also especially noteworthy is that they replace both PFAS-related triflates and nonaflates, which are today out of favor due to recent government regulations. The new complex based on the BippyPhos ligand is used at low loadings and under aqueous micellar conditions. Moreover, it is easily prepared and stable to long term storage. DFT calculations on the OAC precatalyst compare well with the X-ray structure of the crystals with π-complexation to the aromatic system of the ligand and also confirm the NMR data showing a mixture of conformers in solution that differ from the X-ray structure in rotation of the phenyl and t-butyl ligand substituents. An extensive variety of coupling partners, including pharmaceutically relevant APIs, readily participate under mild and environmentally responsible reaction conditions.

Implementation of a national HIV pre-exposure prophylaxis service is associated with changes in characteristics of people with newly diagnosed HIV: a retrospective cohort study.

OBJECTIVES: To review characteristics of individuals newly diagnosed with HIV following implementation of a national pre-exposure prophylaxis (PrEP) programme (comprehensive PrEP services, delivered in sexual health clinics) to inform future delivery and broader HIV prevention strategies. METHODS: We extracted data from national HIV databases (July 2015-June 2018). We compared sociodemographic characteristics of individuals diagnosed in the period before and after PrEP implementation, and determined the proportion of 'potentially preventable' infections with the sexual health clinic-based PrEP delivery model used. RESULTS: Those diagnosed with HIV before PrEP implementation were more likely to be male (342/418, 81.8% vs 142/197, 72.1%, p=0.005), be white indigenous (327/418, 78.2% vs 126/197, 64.0%, p<0.001), report transmission route as sex between men (219/418, 52.4% vs 81/197, 41.1%, p=0.014), and have acquired HIV in the country of the programme (302/418, 72.2% vs 114/197, 57.9% p<0.001) and less likely to report transmission through heterosexual sex (114/418, 27.3% vs 77/197, 39.1%, p=0.002) than after implementation.Pre-implementation, 8.6% (36/418) diagnoses were 'potentially preventable' with the PrEP model used. Post-implementation, this was 6.6% (13/197), but higher among those with recently acquired HIV (49/170, 28.8%). Overall, individuals with 'potentially preventable' infections were more likely to be male (49/49, 100% vs 435/566, 76.9%, p<0.001), aged <40 years (37/49, 75.5% vs 307/566, 54.2%, p=0.004), report transmission route as sex between men (49/49, 100% vs 251/566, 44.3%, p<0.001), have previously received post-exposure prophylaxis (12/49, 24.5% vs 7/566, 1.2%, p<0.001) and less likely to be black African (0/49, 0% vs 67/566, 11.8%, p=0.010) than those not meeting this definition. CONCLUSIONS: The sexual health clinic-based national PrEP delivery model appeared to best suit men who have sex with men and white indigenous individuals but had limited reach into other key vulnerable groups. Enhanced models of delivery and HIV combination prevention are required to widen access to individuals not benefiting from PrEP at present.

Association between rectal gonorrhoea and HIV incidence in men who have sex with men: a meta-analysis.

BACKGROUND: Incidence of rectal gonorrhoea (GC) has been hypothesised as a correlate of HIV exposure in prevention trials of men who have sex with men (MSM). High rectal GC incidence in MSM trials of new biomedical prevention drugs may provide supportive evidence for ongoing HIV risk. Empirical evidence of correlation between rectal GC and HIV incidence is needed to assess whether high rectal GC rates reliably correlate with high risk of HIV. METHODS: Rectal GC and HIV are routinely tested in sexual health clinics (SHCs) throughout England. Through routine surveillance data collected at visits to SHCs, we assessed HIV incidence and new rectal GC diagnoses in repeat visits by HIV-negative MSM between 2011 and 2018, predating widespread roll-out of pre-exposure prophylaxis. Meta-analysis regression assessed population-level association between HIV and rectal GC incidence over time. FINDINGS: Between 2011 and 2018, HIV and rectal GC incidence was assessed in 541 056 HIV-negative MSM attending SHCs in England. HIV incidence among MSM attending SHCs fell from 1.26/100 person-years (PYs) in 2011 to 0.28/100 PYs in 2018. Rectal GC rates increased from 3.5/100 PYs to 11.1/100 PYs over the same period. The rate of HIV incidence decreased by 22.3% for each percent increase in rectal GC (95% CI -30.8 to -14.7, p<0.001). INTERPRETATION: Among the population of MSM attending SHCs in England, rectal GC rates increased substantially while HIV incidence rates decreased between 2011 and 2018. HIV incidence likely decreased through expanded HIV testing, prompt antiretroviral treatment (ART) initiation and increased viral suppression in persons living with HIV, interventions that did not decrease rectal GC. Rectal GC may not be an ideal proxy for HIV incidence in trials, as HIV exposure risk is complex and context dependent, given effective HIV prevention interventions in MSM.

No widespread dissemination of Chlamydia trachomatis diagnostic-escape variants and the impact of Neisseria gonorrhoeae positivity on the Aptima Combo 2 assay.

OBJECTIVES: A Finnish Chlamydia trachomatis (CT) new variant was detected in 2019 that escaped detection in the Hologic Aptima Combo 2 (AC2) assay due to a C1515T mutation in the CT 23S rRNA target region. Reflex testing of CT-negative/CT-equivocal specimens as well as those positive for Neisseria gonorrhoeae (NG) with the Hologic Aptima CT (ACT) assay was recommended to identify any CT variants. METHODS: From June to October 2019, specimens with discrepant AC2/ACT CT results were submitted to Public Health England and screened for detectable CT DNA using an inhouse real-time (RT)-PCR. When enough DNA was present, partial CT 23S rRNA gene sequencing was performed. Analysis of available relative light units and interpretative data was performed. RESULTS: A total of 317 discordant AC2/ACT specimens were collected from 315 patients. Three hundred were tested on the RT-PCR; 53.3% (n=160) were negative and 46.7% (n=140) were positive. Due to low DNA load in most specimens, sequencing was successful for only 36 specimens. The CT 23S rRNA wild-type sequence was present in 32 specimens, and two variants with C1514T or G1523A mutation were detected in four specimens from three patients. Of the discordant specimens with NG interpretation, 36.6% of NG-negative/CT-negative AC2 specimens had detectable CT DNA on the inhouse RT-PCR vs 53.3% of NG-positive/CT-negative specimens. CONCLUSIONS: No widespread dissemination of AC2 diagnostic-escape CT variants has occurred in England. We however identified the impact of NG positivity on the discordant AC2/ACT specimens; a proportion appeared due to NG positivity and the associated NG signal, rather than any diagnostic-escape variants or low DNA load. Several patients with gonorrhoea may therefore receive false-negative AC2 CT results. Single diagnostic targets and multiplex diagnostic assays have their limitations such as providing selection pressure for escape mutants and potentially reduced sensitivity, respectively. These limitations must be considered when establishing diagnostic pathways.

Factors associated with reporting antibiotic use as STI prophylaxis among HIV PrEP users: findings from a cross-sectional online community survey, May-July 2019, UK.

OBJECTIVES: The use of antibiotics as pre-exposure or postexposure prophylaxis for sexually transmitted infection (STI) prevention (STI prophylaxis) is not currently recommended in the UK, but there is evidence that self-prescribing occurs among those at greatest risk. We present the prevalence and factors associated with STI prophylaxis among a community sample of HIV pre-exposure prophylaxis (PrEP) users. METHODS: The 2019 online PrEP User Survey ran between 17 May and 1 July. Eligible participants included UK residents reporting HIV PrEP use or having tried to obtain HIV PrEP since January 2017. STI prophylaxis use was defined as reporting buying antibiotics to prevent STIs, either privately or through the internet; this question was only asked to HIV PrEP users. Factors associated with STI prophylaxis use were assessed using univariable and multivariable logistic regression. RESULTS: Overall, 9% (167/1856) of HIV PrEP users reported STI prophylaxis use; 97% were gay or bisexual men, 84% reported white ethnicity, 55% resided in London and 69% were aged ≥35 years. Factors associated with STI prophylaxis included: reporting ≥5 compared with 1-4 condomless sex partners in the past 6 months (12% vs 5.6%, adjusted odds ratio (aOR)=1.80; 95% CI 1.22 to 2.64), reporting chemsex drug use compared with no sexualised drug use in the past 12 months (13% vs 6.0%, aOR=1.88; 95% CI 1.20 to 2.93) and reporting an STI diagnosis in the past 12 months (12% vs 6.6%, aOR=1.54; 95% CI 1.08 to 2.18). Variables not significant in multivariable analyses included: ethnicity, age, residence and HIV PrEP sourcing. CONCLUSIONS: Approximately 1 in 10 HIV PrEP users from this community sample reported self-prescribed STI prophylaxis. STI prophylaxis was associated with sexual behaviour known to facilitate STI transmission and with a history of recent STIs acquisition. Given the potential risk of antimicrobial resistance, sexual health clinicians should consider asking attendees, especially HIV PrEP users, about the use of antibiotics as STI prophylaxis, to inform appropriate counselling, testing and management.

Preparing for PrEP: estimating the size of the population eligible for HIV pre-exposure prophylaxis among men who have sex with men in England.

OBJECTIVES: The size of the population of men who have sex with men (MSM) who may be eligible for HIV pre-exposure prophylaxis (HIV-PrEP) in England remains unknown. To plan for a national PrEP implementation trial, we estimated the number of MSM attending sexual health clinics (SHCs) that may be eligible for HIV-PrEP in England. METHODS: Sexually transmitted infection (STI) surveillance data from 2010 to 2015 from the GUMCAD surveillance system were used to estimate the annual number of HIV-negative MSM who may be eligible for HIV-PrEP in England. Based on national eligibility criteria, we identified HIV-negative MSM attending SHCs with a HIV-negative test in the past year and used diagnosed bacterial STI (past year) in this group as a proxy for condomless sex and eligibility for HIV-PrEP. We estimated HIV incidence per 100 person-years (py) in these groups in 2014. RESULTS: During 2010-2015, the number of HIV-negative MSM attending SHCs with a HIV-negative test in the past year doubled from 14 643 to 29 023, and HIV incidence in this group was 1.9 (95% CI 1.6 to 2.2) per 100 py in 2014. In the same period, the subgroup with a bacterial STI diagnosis (past year), and therefore considered potentially eligible for HIV-PrEP in this analysis, increased from 4365 (30%) to 10 276 (35%). HIV incidence in this subgroup was 3.3 (95% CI 2.7 to 4.0) per 100 py in 2014. CONCLUSIONS: In 2015, approximately 10 000 HIV-negative MSM were considered potentially eligible for HIV-PrEP based on clinic history in GUMCAD. These data were used to inform the initial recruitment target for the PrEP Impact Trial and will inform future evaluations at a population level.

Person-centred care and HIV: challenges and solutions.

Person-centred consultations (PCCs) are fundamental to effective healthcare communication, and its use is embedded within key clinical guidance. There are three aspects to PCC: use of the best available research evidence, clinical expertise of the clinician and the patient's circumstances, goals, values and wishes. Balancing theses three aspects in the context of HIV prevention and management can be challenging, and we use three case examples to highlight these.

Attitudes to, and experience of, pooled sampling for sexually transmitted infection testing: a web-based survey of English sexual health services.

Chlamydia trachomatis and Neisseria gonorrhoeae testing guidance recommends extragenital screening with locally validated nucleic acid amplification tests, with anatomical sites tested separately. Evidence supports multi-patient combined aliquot pooled sampling (PS) for population screening; evidence for within-patient PS is sparse. Within-patient PS could be more cost-effective for triple-site testing, but requires distinct clinical pathways and consideration over loss of information to guide risk assessments and treatment. We explored PS attitudes and practices amongst clinicians in England. A cross-sectional web-based survey was distributed to clinical leads of sexual health services throughout England in February 2016. Fifty-two (52/216, 23%) services responded. One service reported current within-patient PS and two were awaiting implementation. Of the 49 services not pooling, five were considering implementation. Concerns raised included the inability to distinguish infection site(s) (36/52, 69%), absence of national guidance (34/52, 65%) and reduced assay performance (18/52, 34%). Only 8/52 (15%) considered the current level of evidence sufficient to support PS, with 40/52 (77%) requesting further validation studies and 39/52 (77%) national guidance. PS was rarely used by respondents to this survey, although the response rate was low. The clinical challenges presented by PS need to be addressed through further development of the evidence base.