Direct switch from an efavirenz-based regimen to intramuscular long-acting cabotegravir plus rilpivirine: A case report.

Switching from oral antiretroviral treatment to intramuscular (IM) cabotegravir (CAB) + rilpivirine (RPV) has an optional oral lead-in to ensure tolerability. The British HIV Association guidelines advise against directly switching from oral antiretroviral (ART) combinations containing strong/moderate cytochrome inducers like efavirenz (EFV) to IM CAB + RPV. EFV has a prolonged elimination half-life, leading to a residual induction of UGT1A1 and CYP3A4 after discontinuation. These enzymes are responsible for CAB and RPV metabolism and their induction might lead to sub-optimal concentrations of CAB and RPV, risking drug resistance. When switching from EFV to oral CAB + RPV, the ATLAS and ATLAS 2M studies showed reduced RPV concentrations but with maintained viral suppression during the oral lead-in and subsequent long-acting injectable (LAI) phases. Also, a recent pharmacokinetic modelling study indicated reduced RPV concentrations, without viral implication, when switching from EFV to IM CAB + RPV. However, there are limited real-world data on direct switching from EFV-based therapy to long-acting IM CAB + RPV. We describe a case where oral intake was impossible in a critical care scenario, switching from emitricitabine/tenofovir-DF (FTC/TDF) 200/245 mg + 600 mg EFV to IM CAB + RPV for treatment optimisation.

Mpox in people with advanced HIV infection: a global case series.

BACKGROUND: People living with HIV have accounted for 38-50% of those affected in the 2022 multicountry mpox outbreak. Most reported cases were in people who had high CD4 cell counts and similar outcomes to those without HIV. Emerging data suggest worse clinical outcomes and higher mortality in people with more advanced HIV. We describe the clinical characteristics and outcomes of mpox in a cohort of people with HIV and low CD4 cell counts (CD4 <350 cells per mm3). METHODS: A network of clinicians from 19 countries provided data of confirmed mpox cases between May 11, 2022, and Jan 18, 2023, in people with HIV infection. Contributing centres completed deidentified structured case report sheets to include variables of interest relevant to people living with HIV and to capture more severe outcomes. We restricted this series to include only adults older than 18 years living with HIV and with a CD4 cell count of less than 350 cells per mm3 or, in settings where a CD4 count was not always routinely available, an HIV infection clinically classified as US Centers for Disease Control and Prevention stage C. We describe their clinical presentation, complications, and causes of death. Analyses were descriptive. FINDINGS: We included data of 382 cases: 367 cisgender men, four cisgender women, and ten transgender women. The median age of individuals included was 35 (IQR 30-43) years. At mpox diagnosis, 349 (91%) individuals were known to be living with HIV; 228 (65%) of 349 adherent to antiretroviral therapy (ART); 32 (8%) of 382 had a concurrent opportunistic illness. The median CD4 cell count was 211 (IQR 117-291) cells per mm3, with 85 (22%) individuals with CD4 cell counts of less than 100 cells per mm3 and 94 (25%) with 100-200 cells per mm3. Overall, 193 (51%) of 382 had undetectable viral load. Severe complications were more common in people with a CD4 cell count of less than 100 cells per mm3 than in those with more than 300 cells per mm3, including necrotising skin lesions (54% vs 7%), lung involvement (29% vs 0%) occasionally with nodules, and secondary infections and sepsis (44% vs 9%). Overall, 107 (28%) of 382 were hospitalised, of whom 27 (25%) died. All deaths occurred in people with CD4 counts of less than 200 cells per mm3. Among people with CD4 counts of less than 200 cells per mm3, more deaths occurred in those with high HIV viral load. An immune reconstitution inflammatory syndrome to mpox was suspected in 21 (25%) of 85 people initiated or re-initiated on ART, of whom 12 (57%) of 21 died. 62 (16%) of 382 received tecovirimat and seven (2%) received cidofovir or brincidofovir. Three individuals had laboratory confirmation of tecovirimat resistance. INTERPRETATION: A severe necrotising form of mpox in the context of advanced immunosuppression appears to behave like an AIDS-defining condition, with a high prevalence of fulminant dermatological and systemic manifestations and death. FUNDING: None.

Clinical characteristics of mpox infection in individuals who received a first dose of modified vaccinia Ankara immunisation.

INTRODUCTION: A key part of the response to the mpox (monkeypox) epidemic has been the vaccination campaign targeted at gay, bisexual and other men who have sex with men (GBM), including people living with HIV (PLWH). METHODS: We undertook a single-site, retrospective analysis of individuals who received a single dose of modified vaccinia Ankara (MVA-BN) prior to the onset of mpox symptoms. Demographics, clinical characteristics and patient management were analysed. RESULTS: Of 10 068 individuals who received a first dose of the MVA-BN vaccination, 15 (0.15%) developed mpox subsequently. All individuals identified were GBM with 12/15 (80%) on Pre-exposure prophylaxis (PrEP) and 3/15 (20%) PLWH. Median time from MVA-BN inoculum to mpox symptoms was 4 days (IQR 3-9), systemic symptoms and supportive medical treatment required were common (11/15 patients, 73%) and all had localising skin lesions. One individual required hospitalisation. CONCLUSIONS: Although clinical presentation was similar to unvaccinated cohorts, we observed low numbers of mpox cases following a first dose of MVA-BN vaccination. Larger, multicentric studies are needed to further evaluate vaccination failure and immunity duration.

Infectious Proctitis due to Human Mpox.

We describe 2 cases of infectious proctitis secondary to human monkeypox in patients presenting with rectal pain. These cases highlight the importance of multidisciplinary management of monkeypox and in expanding case definitions and enabling clinical recognition in patients presenting without skin rash.

Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis.

BACKGROUND: Historically, human monkeypox virus cases in the UK have been limited to imported infections from west Africa. Currently, the UK and several other countries are reporting a rapid increase in monkeypox cases among individuals attending sexual health clinics, with no apparent epidemiological links to endemic areas. We describe demographic and clinical characteristics of patients diagnosed with human monkeypox virus attending a sexual health centre. METHODS: In this observational analysis, we considered patients with confirmed monkeypox virus infection via PCR detection attending open-access sexual health clinics in London, UK, between May 14 and May 25, 2022. We report hospital admissions and concurrent sexually transmitted infection (STI) proportions, and describe our local response within the first 2 weeks of the outbreak. FINDINGS: Monkeypox virus infection was confirmed in 54 individuals, all identifying as men who have sex with men (MSM), with a median age of 41 years (IQR 34-45). 38 (70%) of 54 individuals were White, 26 (48%) were born in the UK, and 13 (24%) were living with HIV. 36 (67%) of 54 individuals reported fatigue or lethargy, 31 (57%) reported fever, and ten (18%) had no prodromal symptoms. All patients presented with skin lesions, of which 51 (94%) were anogenital. 37 (89%) of 54 individuals had skin lesions affecting more than one anatomical site and four (7%) had oropharyngeal lesions. 30 (55%) of 54 individuals had lymphadenopathy. One in four patients had a concurrent STI. Five (9%) of 54 individuals required admission to hospital, mainly due to pain or localised bacterial cellulitis requiring antibiotic intervention or analgesia. We recorded no fatal outcomes. INTERPRETATION: Autochthonous community monkeypox virus transmission is currently observed among MSM in the UK. We found a high proportion of concomitant STIs and frequent anogenital symptoms, suggesting transmissibility through local inoculation during close skin-to-skin or mucosal contact, during sexual activity. Additional resources are required to support sexual health and other specialist services in managing this condition. A review of the case definition and better understanding of viral transmission routes are needed to shape infection control policies, education and prevention strategies, and contact tracing. FUNDING: None.

Correlation between different equations to calculate free testosterone for improved detection of hypogonadism in people living with HIV.

The diagnosis of hypogonadism in people living with HIV (PLWH) remains challenging by the lack of a standardised diagnostic algorithm. Since sexual hormone-binding globulin levels are commonly increased in PLWH, guidelines recommend assessing free testosterone (FT) along with total testosterone levels. We compared different online equations available to estimate FT levels and found a good correlation amongst all algorithms. Estimating FT levels increased diagnostic accuracy of hypogonadism and therefore should be encouraged in clinical practice in PLWH with clinical symptoms of hypogonadism, even when total testosterone levels are normal.

Delivering specialised care to people ageing with HIV in the UK: experience and evolution of services from 2009 to 2019.

BACKGROUND: The introduction of antiretrovirals has resulted in a demographic shift with an increasing proportion of people living with HIV older than 50 years and a change in the spectrum of diseases affecting this population. A specialised clinical service dedicated to older people living with HIV was implemented at Chelsea and Westminster Hospital, London, UK in 2009, following training of health-care providers in HIV, ageing, comorbidity, and polypharmacy management. We report the results of a service evaluation reviewing 10 years of activity of this specialised clinic, including lessons to be applied in routine practice. METHODS: We estimated the prevalence of multimorbidity and polypharmacy and described algorithms devised for use across our HIV outpatient services following implementation of the specialised clinical pathway. The service evaluation was approved by our local clinical governance system and data relative to the period 2009-19 were collected on a secured trust database. FINDINGS: Dedicated time was created for senior and junior doctors, a nurse, and a pharmacy to create clinical appointments for older people living with HIV referred by all service care providers. The team would review different clinical scenarios, book follow-up appointments to review results, refer to different specialists or to complex multidisciplinary teams when necessary. 744 people with HIV aged 50 years and older attended our services (93% [691] male, 7·1% [53] female; mean age 56·5 years [SD 5·5]; 84·2% [622] White, 7·5% [56] Black, 0·9% [7] Asian, 7·5% [56] other race or ethnicity). The prevalence of multimorbidity was 69·3% and of polypharmacy was 46·6%. The most common comorbidities were vitamin D deficiency (428 of 690, 62%), dyslipidaemia (373, 50·1%), hypertension (157, 21·5%), depressive or anxious disorders (117, 15·8%), osteoporosis (91, 12·2%), obesity (98, 13·2%), chronic kidney disease (56, 7·5%), and diabetes (43, 5·7%). Patients with dyslipidaemia, osteoporosis, and metabolic disorders were referred to a live well pathway clinic focusing on targeted lifestyle interventions, including diet and physical exercise, under the supervision of a dietician and a physiotherapist. INTERPRETATION: We have described how our HIV over-50 clinic was organised and implemented, and we reported data showing high rates of comorbidities and polypharmacy, which led to the establishment of a specialised care pathway for all HIV care providers and to the implementation of further joint HIV and specialty clinics (cardiology, metabolic, menopause, nephrology, neurology, and geriatric). FUNDING: None.

Complex PrEP: the factors requiring consultant-led review of PrEP users.

INTRODUCTION: HIV-1 pre-exposure prophylaxis (PrEP) has been available in England since March 2020 on the National Health Service using generic emtricitabine and tenofovir disoproxil. 56 Dean Street (56DS) provided PrEP through (1) additional private care from September 2015, estimated to be providing 11% of England's PrEP in 2019; and (2) the IMPACT trial, as well as monitoring those self-sourcing PrEP. Providing PrEP at scale through a nurse-led service required a safety net for complex individuals. 56DS introduced a consultant-led PrEP outpatient service, the PrEP review clinic, in January 2018 and we report the outcomes of this service. METHODS: We present a retrospective case note review of the PrEP review clinic with descriptive outcomes from 26 January 2018 to 20 December 2019. Reason for referral, demographics, PrEP management and PrEP discontinuations were recorded. RESULTS: 13 980 unique users accessed PrEP from 56DS during the two year evaluation period. 220 individuals were seen in the PrEP review clinic. Majority of patients were referred for renal issues (114 of 220, 51.8%), followed by side effects (59 of 220, 26.8%) and comorbidities (38 of 220, 17.2%). Of those with renal issues, 89 (out of 114, 78.1%) users were referred for an abnormal estimated glomerular filtration rate (eGFR). 35 (out of 114, 30.7%) PrEP users had an eGFR between 45 and 59 mL/min/1.73 m2, of whom 2 (5.7%) discontinued PrEP. Majority of users were advised to stop supplements±switch to event-based dosing (24 of 35, 68.6%). Ten PrEP users were referred with an eGFR between 30 and 44 mL/min/1.73 m2; 4 (40%) stopped or did not start PrEP and 6 (60%) were asked to stop supplements±switch to event-based dosing. DISCUSSION: A small proportion of PrEP users have complex PrEP issues. Methods to manage renal dysfunction with PrEP included stopping supplements and switching to event-based dosing. Those with side effects were managed with an array of options, with only modest effectiveness. Other PrEP options are needed to support those with toxicities or intolerances.

Evaluation of a Clinic Dedicated to People Aging with HIV at Chelsea and Westminster Hospital: Results of a 10-Year Experience.

Successful management of HIV infection as a chronic condition has resulted in a demographic shift where the proportion of people living with HIV (PLWH) older than 50 years is steadily increasing. A dedicated clinic to PLWH older than 50 years was established at Chelsea and Westminster Hospital in January 2009 and then extended to HIV services across the directorate. We report the results of a service evaluation reviewing 10 years of activities of this clinic between January 2009 and 2019. We aimed to estimate the prevalence of major noninfectious comorbidities, polypharmacy (≥5 medications), and multimorbidity (≥2 non-HIV-related comorbidities) and describe algorithms devised for use in HIV outpatient clinics across the directorate. A cohort of 744 PLWH older than 50 years attending this service were analyzed (93% male; mean age of 56 ± 5.5 years; 84% white ethnicity); 97.7% were on antiretroviral treatment and 95.9% had undetectable HIV-RNA at the time of evaluation. The most common comorbidities diagnosed were dyslipidemia (50.1%), hypertension (21.5%), mental health disorders (depression and/or anxiety disorders, 15.7%), osteoporosis (12.2%), obesity (11.9%), chronic kidney disease (7.5%), and diabetes (5.8%). Low vitamin D levels were found in 62% of patients [43% with vitamin D deficiency (<40 mmol/liter) and 57% with vitamin D insufficiency (40-70 mmol/liter)]. The overall prevalence of polypharmacy and multimorbidity was 46.6% and 69.3%, respectively. This study showed significant rates of non-HIV-related comorbidities and polypharmacy in PLWH older than 50 years, leading on to the implementation of clinical care pathways and new joint HIV/specialty clinics (cardiology, nephrology, neurology, metabolic, menopause, and geriatric) to improve prevention, diagnosis, and management of major comorbidities in people aging with HIV.

Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes.

INTRODUCTION: Preexposure prophylaxis (PrEP) is contributing to achieve a reduction in HIV diagnoses in men having sex with men (MSM). Albeit infrequent, HIV infections in the context of recent PrEP exposure represent a clinical challenge. METHODS: Data on recent PrEP use and possible reasons leading to HIV infection were analysed in individuals newly diagnosed with HIV at 56 Dean Street clinic in 2016-2020. Demographics, immune-virological parameters, genotypic resistance test results and treatment management in this group were compared with those not reporting recent PrEP exposure using Mann-Whitney U test and Fisher's exact test. RESULTS: Fifty-two of 1030 (5%) individuals reported recent PrEP exposure at HIV diagnosis; 98% were MSM, median age 34 years (interquartile range [IQR] 28-42), 65% of white ethnicity, 65% non-UK-born. 35% reported PrEP intake the day before testing HIV positive, 46% reported sub-optimal PrEP adherence since their last negative HIV test result. Thirty-three of 52 (63%) were self-sourcing PrEP and 9/52 (17%) reported issues with its supply. Recent PrEP use was associated to lower HIV viral load and higher CD4+ cell count at baseline than in counterparts non-recently exposed to PrEP (P < 0.01). M184V mutation was harboured more commonly in the recent PrEP use group (30% vs. 1%, P < 0.01). The proportion of individuals recently exposed to PrEP among those diagnosed with HIV rose sharply, reaching 21% in the first semester of 2020. Viral suppression was achieved by all patients intensified from PrEP to antiretroviral treatment (ART) who remained in care at week 24. DISCUSSION: Rapid PrEP intensification to ART allowed to achieve high rates of HIV viral suppression despite significant rates of M184V mutation harboured in those newly diagnosed with HIV and reporting recent PrEP exposure.

The success of HIV combination prevention: The Dean Street model.

The 56 Dean Street combination prevention model, a strong engagement with the LGBTQI community and flexible services adapted to users' changing needs led to an 80% drop in HIV diagnoses in gay, bisexual and other men who have sex with men (GBMSM) from 2015 to 2017. We describe the service changes at 56 Dean Street since 2012 which resulted in an increase in the frequency of HIV testing, the introduction of pre-exposure prophylaxis, earlier HIV diagnosis and a shorter time to viral suppression in those living with HIV. This model could be adapted to deliver similar results in those settings of high HIV prevalence among GBMSM and where access to technological innovation in healthcare and engagement with the community can be achieved.

Clinical and serological outcomes in patients treated with oral doxycycline for early neurosyphilis.

OBJECTIVES: Penicillin-based antibiotic treatment for syphilis infection with CNS involvement (early neurosyphilis) is not always a suitable treatment option. We compared outcomes of patients diagnosed with early neurosyphilis and treated with doxycycline or procaine G penicillin. METHODS: Serological and clinical outcomes were analysed in patients diagnosed with early neurosyphilis between January 2015 and October 2019 at 56 Dean Street, a combined sexual health and HIV service based in London, UK. Acute onset of CNS, ocular and/or otic symptomatology and a documented seroconverting syphilis serology or a >4-fold increase in rapid plasma reagin ('RPR)' test titre within the previous 12 months were criteria used to define a case. Mann-Whitney U-test and χ2 tests were used to test distributions between baseline characteristics and outcomes according to treatment administered. RESULTS: Eighty-seven patients were included: median age = 35 years (IQR = 31-45), 98% MSM, 79% white ethnicity, 53% HIV-1 positive and 40% previously diagnosed with syphilis at any stage. They were treated exclusively with either intramuscular (IM) procaine G penicillin (71%) or oral doxycycline (18%). Patients received doxycycline treatment over a penicillin-based regimen due to IM treatment declined (31%), inability to attend for IM injections (31%) or penicillin allergy (19%). Serological response was achieved by all patients; 91% reported full symptom resolution at 30 days from end of treatment. Similar rates of clinical and serological response and seroreversion were observed in the groups treated with procaine G penicillin versus doxycycline. CONCLUSIONS: The clinical and serological outcomes seen with penicillin-based versus doxycycline treatments were similar. A randomized controlled trial is needed to establish the effectiveness of doxycycline in the treatment of early neurosyphilis.

COVID-19 restrictions and changing sexual behaviours in HIV-negative MSM at high risk of HIV infection in London, UK.

OBJECTIVES: The COVID-19 pandemic and its related restrictions have affected attendance to and delivery of UK sexual healthcare services (SHS). We surveyed the impact on sexual behaviour of men having sex with men (MSM) to inform future SHS provision. METHODS: We conducted a cross-sectional, anonymous, web-based survey among HIV-negative MSM at high risk of HIV infection who attended 56 Dean Street, a sexual health and HIV clinic. The survey was conducted over a 7-day period in August 2020. Data on sociodemographic characteristics, sexual behaviour and related mental well-being experienced during lockdown (defined as 23 March-30 June 2020) were extracted. Categorical and non-categorical variables were compared according to HIV pre-exposure prophylaxis (PrEP) use. RESULTS: 814 MSM completed the questionnaire: 75% were PrEP users; 76% reported they have been sexually active, of which 76% reported sex outside their household. 75% reported fewer partners than prior to lockdown. Isolation/loneliness (48%) and anxiety/stress (27%) triggered sexual activity, and 73% had discussed COVID-19 transmission risks with their sexual partners. While 46% reported no change to emotions ordinarily experienced following sex, 20% reported guilt for breaching COVID-19 restrictions. 76% implemented one or more changes to their sexual behaviour, while 58% applied one or more steps to reduce COVID-19 transmission during sex. 36% accessed SHS and 30% reported difficulties in accessing testing/treatment. Of those who accessed SHS, 28% reported an STI diagnosis. PrEP users reported higher partner number, engagement in 'chemsex' and use of SHS than non-PrEP users. CONCLUSIONS: COVID-19 restrictions had a considerable impact on sexual behaviour and mental well-being in our survey respondents. High rates of sexual activity and STI diagnoses were reported during lockdown. Changes to SHS provision for MSM must respond to high rates of psychological and STI-related morbidity and the challenges faced by this population in accessing services.

Rapid ART start in early HIV infection: Time to viral load suppression and retention in care in a London cohort.

OBJECTIVES: Rapid antiretroviral therapy (ART) initiation is recommended in early HIV infection (EHI), even in the absence of baseline viral resistance test result. We analysed time to viral suppression according to ART regimen started in a cohort of patients diagnosed with EHI. METHODS: Clinical records of individuals consecutively diagnosed with EHI between July 2016-June 2018 were reviewed. The distribution of clinical, virological and immunological factors was compared in treatment groups using the Mann-Whitney U-test. RESULTS: 262 individuals (97% MSM) were diagnosed with EHI. 58% of patients agreed to start ART within 14 days of diagnosis. Tenofovir-based combinations were prescribed to all patients. DRV/b was the most commonly prescribed third agent (78%), when genotypic resistance testing was not available at time of ART choice. Switching to INSTI was encouraged once VRT became available and 27% switched from DRV/b to INSTI (mainly RAL) within 28 days from ART start. Those receiving INSTI were more likely to have a baseline viral load exceeding 1 million HIV-1 RNA copies/mL compared with those starting with DRV/b. Rapid start with INSTI regimens resulted in quicker viral suppression than when DRV/b was chosen in EHI, even when that was subsequently switched to INSTI. Retention in care following rapid ART start was achieved by all patients at 24 weeks. CONCLUSIONS: Starting an INSTI-based ART combination was associated with quicker viral suppression than when a protease inhibitor-based combination was chosen. No differences in the achievement of viral suppression or in retention in care were observed.

High rates of unprotected anal sex and use of generic direct-acting antivirals in a cohort of MSM with acute HCV infection.

The role of condomless anal intercourse (CAI) as a driver for the epidemic of hepatitis C in MSM is still debated. Timely access to direct-acting antivirals (DAA) could represent an essential strategy to tackle this. Case notes of MSM diagnosed with acute hepatitis C (AHC) between July 2016 and June 2017 in a sexual health clinic in London were included. Behavioural data on sexual practices and STI monitoring in the 6 months prior to AHC diagnosis were collected. DAA routes of access and timing from AHC diagnosis to start of treatment were analysed. A total of 60 individuals were enrolled (median age 39 years, IQR = 33-46, 62% HIV co-infected, 72% genotype 1a). CAI was reported by 97%, drug use prior to or during sex by 73%; 46% was diagnosed with a rectal STI and 29% with syphilis. About 37% did not report any HCV risk factors other than condomless anal sex. About 36% had a new rectal STI in the 6 months following AHC. About 82% accessed DAA treatment and median time from AHC to DAA start was 278 days for those following the NHS standard of care route, 132 days for those accessing DAA via participation in trials and 114 for those who had self-sourced DAA online (P < 0.0011). SVR12 was achieved in 100% of the patients who received DAA treatment.In conclusion, CAI is a significant risk factor for HCV acquisition in MSM, irrespective of their HIV status. Rapid and wider access to treatment with DAA could represent a powerful strategy to reduce onward transmission and risk of reinfection in MSM.

Evolution of a pre-exposure prophylaxis (PrEP) service in a community-located sexual health clinic: concise report of the PrEPxpress.

Screening and treatment of sexually transmissible infections, including HIV, are free in the UK nations; pre-exposure prophylaxis (PrEP) became free in England in October 2017 through the PrEP Impact trial. Doctor-led PrEP clinics started at 56 Dean Street in September 2015, with the drug purchased privately at full price. The service was expanded to other staff to support initiation and monitoring of increasing numbers of attendees purchasing PrEP from online pharmacies. Nonetheless, when the clinic was given a target of 1700 for the PrEP Impact trial, it was clear this could not be achieved in a timely manner through 56 Dean Street alone. To prepare for the trial, all staff with HIV testing competencies were trained in good clinical practice and trial-specific procedures, and a patient group directive was approved to facilitate nurse prescribing and dispensing. Electronic pro formas to capture eligibility for starting or continuing PrEP were adapted for the Dean Street Express clinic, with some information collected directly from service users using touch screens. These interventions, together with an update to the 2016 information leaflet developed by the community, enabled enrolment and follow-up of 1700 participants in 4 months. PrEP advice and monitoring were easily accommodated in the 56 Dean Street sexual health service, but did require additional training and approval for nurse prescribing and dispensing drug in order to achieve the target, which still fell short of the demand.