UK guideline for the use of HIV post-exposure prophylaxis 2021.

We present the updated British Association for Sexual Health and HIV (BASHH) guidelines for post-exposure prophylaxis (PEP) to HIV following sexual exposures, occupational exposures and other nonoccupational exposures in the community. This serves as an update to the 2015 BASHH guideline on PEP following sexual exposures and the 2008 Expert Advisory Group on AIDS guidelines on HIV PEP. We aim to provide evidence-based guidance on best clinical practice in the provision, monitoring and support of PEP for the prevention of HIV acquisition following sexual, occupational and other nonoccupational exposures in the community. The guideline covers when to prescribe PEP, what antiretroviral agents to use and how to manage PEP. This includes (i) evidence of PEP efficacy; (ii) evidence relating to individual-level efficacy of antiretroviral therapy to prevent the sexual transmission of HIV; (iii) data on the detectable (transmissible) prevalence of HIV in specific populations; (iv) risk of HIV transmission following different types of sexual and occupational exposure; (v) baseline risk assessment; (vi) drug regimens and dosing schedules; (vii) monitoring PEP; (viii) baseline and follow-up blood-borne virus testing; (ix) the role of PEP within broader HIV prevention strategies, for example, HIV pre-exposure prophylaxis (PrEP). The guideline also covers special scenarios such as PEP in pregnancy, breastfeeding and chronic hepatitis B virus infection, and when PEP should be considered in people using HIV PrEP. The guidelines are aimed at clinical professionals directly involved in PEP provision and other stakeholders in the field. A proforma to assist PEP consultations is included. A public consultation process was undertaken prior to finalizing the recommendations.

Testing for syphilis.

Syphilis is no longer a disease headed for the history books but a disease on the resurgence. Its rising prevalence in populations of all sexualities has moved it from an unlikely differential diagnosis to an important one not to miss. With a latency to symptoms of sometimes many years, syphilis is a key disease to consider and does not need the clinician to attempt to risk assess the patient. This article seeks to equip the jobbing neurologist to recognise the manifestations of syphilis, and to understand the tests available, the interpretation of results and the limitations of testing. We provide an overview approach to assessing and managing these cases, what to expect and where to seek expert opinion and advice.

Factors associated with four atypical cases of congenital syphilis in England, 2016 to 2017: an ecological analysis.

Four isolated cases of congenital syphilis born to mothers who screened syphilis negative in the first trimester were identified between March 2016 and January 2017 compared with three cases between 2010 and 2015. The mothers were United Kingdom-born and had no syphilis risk factors. Cases occurred in areas with recent increases in sexually-transmitted syphilis among women and men who have sex with men, some behaviourally bisexual, which may have facilitated bridging between sexual networks.

Resurgence of congenital syphilis: new strategies against an old foe.

Congenital syphilis is a major global cause of fetal loss, stillbirth, neonatal death, and congenital infection. In 2020, the global rate of congenital syphilis was 425 cases per 100 000 livebirths-substantially higher than WHO's elimination target of 50 cases per 100 000 livebirths. Case rates are rising in many high-income countries, but remain low compared with those in low-income and middle-income settings. This Review aims to summarise the current epidemiology and knowledge on transmission and treatment of syphilis in pregnancy, and proposes measures to reduce the rising incidence seen worldwide. We also describe emerging diagnostic and treatment tools to prevent vertical transmission and improve management of congenital syphilis. Finally, we outline a programme of public health priorities, which include research, clinical, and preventive strategies.

Audit of HIV testing frequency and behavioural interventions for men who have sex with men: policy and practice in sexual health clinics in England.

BACKGROUND: National guidance recommends targeted behavioural interventions and frequent HIV testing for men who have sex with men (MSM). We reviewed current policy and practice for HIV testing and behavioural interventions (BI) in England to determine adherence to guidance. METHODS: 25 sexual health clinics were surveyed using a semistructured audit asking about risk ascertainment for MSM, HIV testing and behavioural intervention policies. Practice was assessed by reviewing the notes of the first 40 HIV-negative MSM aged over 16 who attended from 1 June 2010, in a subset of 15 clinics. RESULTS: 24 clinics completed the survey: 18 (75%) defined risk for MSM and 17 used unprotected anal intercourse (UAI) as an indication of high risk. 21 (88%) offered one or more structured BI. Of 598 notes reviewed, 199 (33%) MSM reported any UAI. BI, including safer sex advice, was offered to and accepted by 251/598 (42%) men. A low proportion of all MSM (52/251: 21%) accepted a structured one-to-one BI as recommended by national guidance and uptake was still low among higher risk MSM (29/107: 27%). 92% (552/598) of men had one or more HIV test over a 1-year period. CONCLUSIONS: In 2010, the number of HIV tests performed met the national minimum standard but structured behavioural interventions were being offered to and accepted by only a small proportion of MSM, including those at a higher risk of infection. Reasons for not offering behavioural interventions to higher risk MSM, whether due to patient choice, a lack of staff training or resource shortage, need to be investigated and addressed.

HTLV seroprevalence in people using HIV pre-exposure prophylaxis in England.

OBJECTIVES: HTLV-1 is predominantly a sexually-transmitted infection but testing is not mentioned in HIV-PrEP guidelines. We ascertained HTLV-1/HTLV-2 seroprevalence amongst HIV-PrEP users in England. METHODS: An unlinked anonymous seroprevalence study. RESULTS: Amongst 2015 HIV-PrEP users, 95% were men, 76% of white ethnicity and 83% had been born in Europe. There were no HTLV-1/HTLV-2 seropositive cases (95% confidence interval 0% - 0.18%). CONCLUSIONS: There were no HTLV positive cases, likely reflecting the demographic of mostly white and European-born individuals. Similar studies are needed worldwide to inform public health recommendations for HIV-PrEP using populations, particularly in HTLV-endemic settings.

Stepping up from opt-out: Achieving 100% uptake antenatal human immunodeficiency virus testing.

All pregnant women in the United Kingdom are offered and encouraged to take up screening for human immunodeficiency virus (HIV), hepatitis B and syphilis, with excellent uptake rates and engagement in care resulting in very few infants being infected with HIV in the United Kingdom. However, in that small number of women who decline testing, there remains an opportunity to offer further support to test and engage them and their baby in care, even if this happens in labour or immediately after birth. In addition, these women may be at increased risk of HIV. Our hospital is in an extremely high prevalence area for HIV, and most untested individuals are of childbearing age. We embarked on a quality improvement project to engage all women delivering at our unit in HIV testing or to test their babies via cord blood at birth. We sought to do this in a constructive and inclusive way, led by the HIV specialist midwife with the support of the HIV antenatal and the hospital senior management teams. Following an initial evaluation, the approach was modified and an innovative approach together with a trusted advocate was used to engage a particularly hard-to-reach group. We have achieved 100% uptake of HIV testing and made two HIV diagnoses that would not otherwise have been made; both in women who reported themselves not to be at risk and both engaged in care and delivered HIV-negative infants.

What do senior genitourinary medicine physicians think of the future of the speciality? A national survey.

Genitourinary Medicine (GUM) is a specialty that has undergone significant change over the past decade. Multiple factors have contributed to this including changes in service models and commissioning landscapes, health service leadership, medical education and changes in the spectrum of our clinical work. The Joint Specialist Committee for GUM at the Royal College of Physicians (RCP) conducted a national survey in December 2019 - January 2020 to understand the changing scope of work for GUM consultants. The survey indicated an increase in clinical complexity alongside a decline in registrar recruitment, staff shortages and service fragmentation. Funding cuts have impacted many services and the majority of consultants feel a return to an NHS commissioning model would be preferable. Despite the many challenges, GUM physicians consider the specialty 'unique, dynamic, friendly and open-minded'. It is clear that senior doctors value the wider clinical, academic and educational opportunities within the specialty.

Use of pritelivir in refractory aciclovir-resistant herpes simplex virus type 2.

Recurrence of mucocutaneous herpes simplex virus (HSV) infections is common in immunosuppressed patients. Thymidine kinase mutations conferring resistance to the antiviral agent aciclovir have been observed in such patients. Recommended second-line therapeutic agents against HSV are associated with significant side effects contributing to disease burden. We present a case of aciclovir-resistant herpes simplex virus 2 (HSV-2) in an immunosuppressed (HIV negative) allogenic peripheral blood stem cell transplant (SCT) recipient which was refractory to second-line therapy. Compassionate acquisition of the novel oral helicase-primase inhibitor pritelivir provided both symptomatic and virological control for the duration of its use. We believe this to be the first clinical use of this therapeutic agent in the United Kingdom.

2018 UK national guideline for the management of donovanosis.

The objective of this guideline is to provide guidance for the diagnosis and management of donovanosis, a now rare sexually transmitted infection. This guidance is primarily for professionals working in UK Sexual Health services (although others may find it useful) and refers to the management of individuals presenting with possible symptoms of donovanosis who are over the age of 16. An updated literature review since the last Clinical Effectiveness Group (CEG) guideline produced for this condition in 2011 has shown few new developments. Most reports in the literature relate to cases of unusual presentations of the condition.

Retrospective analysis of the associations and effectiveness of performing therapeutic drug monitoring in pregnant HIV-positive women in two large centres in Manchester.

There is no proven benefit for the routine use of therapeutic drug monitoring in HIV-positive pregnant women either for improving viral control or preventing mother-to-child transmission. This analysis reviewed a cohort of 171 HIV-positive pregnant women delivering between 1 January 2008 and 28 May 2013 to first establish which baseline characteristics are associated with having therapeutic drug monitoring performed, and whether therapeutic drug monitoring was associated with improved HIV control during pregnancy or mother-to-child transmission. Therapeutic drug monitoring was performed in 39% ( n = 66) of patients; it was associated with baseline characteristics of poor adherence to therapy (therapeutic drug monitoring 23% versus non-therapeutic drug monitoring 10%, p = 0.025) and the use of protease inhibitors (therapeutic drug monitoring 94% versus non-therapeutic drug monitoring 77%, p = 0.005). By multivariate analysis therapeutic drug monitoring was associated with medication alterations during pregnancy (therapeutic drug monitoring 68% versus non-therapeutic drug monitoring 12%, p = < 0.001), but not associated with any difference in viral load breakthrough during pregnancy (therapeutic drug monitoring 12% versus non-therapeutic drug monitoring 7%, p = 0.456) and viral load detectable at birth (therapeutic drug monitoring 14% versus non-therapeutic drug monitoring 9%, p = 0.503). There were no instances of mother-to-child transmission. Therapeutic drug monitoring's association with medication changes is postulated as partially causal in this cohort. There was no evidence of any association with improved control or reduced transmission of HIV to advocate routine therapeutic drug monitoring use.

Real-world persistence with antiretroviral therapy for HIV in the United Kingdom: A multicentre retrospective cohort study.

OBJECTIVES: Persistence with an antiretroviral therapy (ART) regimen for HIV can be defined as the length of time a patient remains on therapy before stopping or switching. We aimed to describe ART persistence in treatment naïve patients starting therapy in the United Kingdom, and to describe differential persistence by treatment regimen. METHODS: We performed a retrospective cohort study at eight UK centres of ART-naïve adults commencing ART between 2012 and 2015. Aggregate data were extracted from local treatment databases. Time to discontinuation was compared for different third agents and NRTI backbones using incidence rates. RESULTS: 1949 patients contributed data to the analysis. Rate of third agent change was 28 per 100 person-years of follow up [95% CI 26-31] and NRTI backbone change of 15 per 100 person-years of follow up [95% CI 14-17]). Rilpivirine, as co-formulated rilpivirine/tenofovir/emtricitabine had a significantly lower discontinuation rate than all other third agents and, excluding single tablet regimens, co-formulated tenofovir/emtricitabine had a significantly lower discontinuation rate than co-formulated abacavir/lamivudine. The reasons for discontinuation were not well recorded. CONCLUSIONS: Treatment discontinuation is not an uncommon event. Rilpivirine had a significantly lower discontinuation rate than other third agents and tenofovir/emtricitabine a lower rate than co-formulated abacavir/lamivudine.

British Association for Sexual Health and HIV: framework for guideline development and assessment.

The Clinical Effectiveness Group of the British Association for Sexual Health has updated their methodology for the production of national guidelines for the management of sexually transmitted infections and related conditions. The main changes are the adoption of the GRADE system for assessing evidence and making recommendations and the introduction of a specific Conflict of Interests policy for Clinical Effectiveness Group members and guideline authors. This new methodology has been piloted during the production of the 2015 British Association for Sexual Health & HIV guideline on the management of syphilis.

UK national guidelines on the management of syphilis 2015.

These guidelines are an update for 2015 of the 2008 UK guidelines for the management of syphilis. The writing group have piloted the new BASHH guideline methodology, notably using the GRADE system for assessing evidence and making recommendations. We have made significant changes to the recommendations for screening infants born to mothers with positive syphilis serology and to facilitate accurate and timely communication between the teams caring for mother and baby we have developed a birth plan. Procaine penicillin is now an alternative, not preferred treatment, for all stages of syphilis except neurosyphilis, but the length of treatment for this is shortened. Other changes are summarised at the start of the guideline.

HIV coreceptor and chemokine ligand gene expression in the male urethra and female cervix.

OBJECTIVE: Isolates with a tropism for the coreceptor CCR5 are the predominant viral strain transmitted following heterosexual transmission. We have investigated coreceptor expression levels within male and female genital epithelia to assess whether selective transmission can be explained by elevated CCR5 expression within the genital epithelia per se. DESIGN: Individuals attending a local genitourinary medicine unit were recruited, and samples of genital epithelia obtained using either a cytobrush (females) or urethral swab (males). Expression of coreceptor and cell marker mRNAs was then determined by reverse transcription (RT)-PCR. METHODS: RNA was recovered from the epithelial cell samples then used as templates in competitive quantitative RT-PCR to measure mRNA expression of key chemokines, coreceptors and cell-type markers in the epithelial cell samples. Cell-surface coreceptor expression was also assessed in a sample of patients using fluorescent cell staining. RESULTS: CXCR4 and CCR3 coreceptors were expressed at significantly higher levels than CCR5 within the female endo- and ectocervix and distal end of the male urethra. Increased levels of cell surface expressed CXCR4 compared to CCR5 was confirmed in samples obtained from the female genital tract by FACS analysis. CONCLUSIONS: The selective transmission of CCR5-tropic viral variants is unlikely to result simply from differential coreceptor abundance at the genital epithelia.