Belgian 2024 guidance on the use of pre-exposure prophylaxis.

OBJECTIVES: We aimed to develop a guidance on the use of pre-exposure prophylaxis (PrEP) for HIV tailored to the Belgian context. METHODS: Different aspects of PrEP care were judged by an expert group of nine Belgian clinicians, seeking consensus for areas of controversies. RESULTS: PrEP should be considered in HIV negative patients at high risk of acquiring HIV. Currently, only oral tenofovir/emtricitabine is available in Belgium for PrEP, which can be used daily, or also event-driven in cisgender men and trans women who are not taking exogenous estradiol-based hormones. Personal counselling directed at medication adherence and sexual health should have a central role in PrEP care. At the initial assessment clinicians should give attention to symptoms of an acute HIV infection, the patients' immunization status and renal function. A regular follow-up must be set up to diagnose HIV seroconversion, treat sexually transmitted infections, and manage side effects of PrEP. CONCLUSION: The Belgian guidance on the use of PrEP provides a point of reference for standard PrEP care in Belgium and will be periodically updated.

Effect of screening for Neisseria gonorrhoeae and Chlamydia trachomatis on incidence of these infections in men who have sex with men and transgender women taking HIV pre-exposure prophylaxis (the Gonoscreen study): results from a randomised, multicentre, controlled trial.

BACKGROUND: Guidelines recommend screening for Neisseria gonorrhoeae and Chlamydia trachomatis at three anatomical sites (urethra, anus, and pharynx) every 3 months (3 × 3) in men who have sex with men (MSM) and transgender women taking HIV pre-exposure prophylaxis (PrEP). We present the first randomised controlled trial to compare the effect of screening versus non-screening for N gonorrhoeae and C trachomatis on the incidence of these infections in MSM and transgender women taking PrEP. METHODS: A multicentre, randomised, controlled trial of 3 × 3 screening for N gonorrhoeae and C trachomatis versus non-screening was done among MSM and transgender women taking PrEP in five HIV reference centers in Belgium. Participants attended the PrEP clinics quarterly for 12 months. N gonorrhoeae and C trachomatis was tested at each visit in both arms, but results were not provided to the non-screening arm, if asymptomatic. The primary outcome was incidence rate of N gonorrhoeae and C trachomatis infections in each arm, assessed in the per-protocol population. Non-inferiority of the non-screening arm was proven if the upper limit of the 95% CI of the incidence rate ratio (IRR) was lower than 1·25. This trial is registered with ClinicalTrials.gov, NCT04269434, and is completed. FINDINGS: Between Sept 21, 2020, and June 4, 2021, 506 participants were randomly assigned to the 3 × 3 screening arm and 508 to the non-screening arm. The overall incidence rate of N gonorrhoeae and C trachomatis was 0·155 cases per 100 person-days (95% CI 0·128-0·186) in the 3 × 3 screening arm and 0·205 (95% CI 0·171-0·246) in the non-screening arm. The incidence rate was significantly higher in the non-screening arm (IRR 1·318, 95% CI 1·068-1·627). Participants in the non-screening arm had a higher incidence of C trachomatis infections and symptomatic C trachomatis infections. There were no significant differences in N gonorrhoeae infections. Participants in the non-screening arm consumed significantly fewer antimicrobial drugs. No serious adverse events were reported. INTERPRETATION: We failed to show that non-screening for N gonorrhoeae and C trachomatis is non-inferior to 3 × 3 screening in MSM and transgender women taking PrEP in Belgium. However, screening was associated with higher antibiotic consumption and had no effect on the incidence of N gonorrhoeae. Further research is needed to assess the benefits and harms of N gonorrhoeae and C trachomatis screening in this population. FUNDING: Belgian Health Care Knowledge Centre.

The value of herpes zoster prevention in people aging with HIV: A narrative review.

OBJECTIVE: Review the evidence on the incidence and impact of herpes zoster among people living with HIV and the potential impact of recombinant zoster vaccine for people aging with HIV. METHODS: Narrative review. RESULTS: Although antiretroviral therapy has substantially reduced the risk of herpes zoster among people living with HIV, they remain at an increased risk compared with the general population. Among people aging with HIV, aging per se is now the main risk factor for herpes zoster. Beyond pain, herpes zoster is also associated with a risk of sight-threatening complications in case of trigeminal involvement, disseminated diseases and stroke. Post-herpetic neuralgia is also a potential threat to the quality of life of people aging with HIV. The recombinant zoster vaccine has demonstrated high and sustained efficacy in the prevention of herpes zoster, post-herpetic neuralgia, and other herpes zoster complications in the general population. Immunogenicity data among people living with HIV with high CD4+ T-cell count and controlled viral load are comparable to those among the general population. Real-life effectiveness data indicate high vaccine efficacy among immunocompromised patients other than people living with HIV. High vaccine price, vaccine hesitancy, and limited disease and vaccine awareness represent potential hurdles for high vaccine uptake among people aging with HIV in Europe. CONCLUSIONS: Herpes zoster, and its complications, is a vaccine-preventable disease of aging people. Given its impact on quality of life, herpes zoster prevention using recombinant zoster vaccine is a safe strategy to be considered in every person aging with HIV.

Diagnostic approach to monkeypox outbreak, a case-control study.

BACKGROUND: An international outbreak of the monkeypox (MPX) virus is ongoing with a different clinical presentation than previously reported. OBJECTIVE: A monocentric retrospective study was designed to investigate clinical predictors of confirmed MPX cases among a group of patients referred for MPX screening. Furthermore, the additional value of performing a real-time polymerase chain reaction (RT-PCR) on multiple anatomical sites was analyzed. METHODS: Between 28/05/2022 and 22/07/2022, the medical records of patients referred for MPX screening were investigated. Patients with positive RT-PCR were defined as cases, while the ones with negative RT-PCR as controls. Multivariable regression analysis was performed to estimate predictors of MPX diagnosis. RESULTS: Among the 141 included patients, 85 (60%) had at least one positive RT-PCR for MPX. Carrying out RT-PCR only on the swab obtained by skin lesion sampling, 7 patients (7/85: 8%) would have been misdiagnosed. Multivariable regression analysis showed significant differences in the independent variables: "being men who have sex with men (MSM)", "living with HIV", "having multiple sexual partners in the last 3 weeks", and "having skin lesions in the anogenital area" for prediction of MPX diagnosis. These four discriminants were used to create a score to improve diagnosis in patients screened for MPX. CONCLUSION: MPX diagnosis was associated with being MSM, living with HIV, having multiple sexual partners, and presenting with anogenital skin lesions. In this study, the derived score had good sensitivity and specificity to predict MPX diagnosis. Finally, performing multi-site swabs for MPX RT-PCR might lower false negative rates.

Impact of COVID-19 on the Belgian HIV epidemic: slowdown of HIV transmission and testing and adaptation of care.

BACKGROUND: To gain insight into the impact of the COVID-19 pandemic and containment measures on the HIV epidemic and services, this study aims to describe HIV trends in 2020 and compare them with previous years. METHODS: Belgian national HIV surveillance data 2017-2020 were analysed for trends in HIV testing, HIV diagnoses, VL measurements, ART uptake and PrEP purchase. Descriptive statistics from 2020 are compared to annual averages from 2017 to 2019 (proportional difference, %). RESULTS: In 2020, 725 HIV infections were diagnosed in Belgium (- 21.5% compared to 2019). The decline was most pronounced during the first lockdown in April-May but also present in July-December. The number of HIV tests performed decreased by 17.6% in 2020, particularly in March-May and October-December (- 57.5% in April and -25.4% in November 2020 compared to monthly 2017-19 numbers). Diagnosis of acute HIV infections decreased by 47.1% in 2020 (n = 27) compared to 2019 (n = 51). Late HIV diagnoses decreased by 24.7% (95% CI [- 40.7%; -9.7%]) in 2020 compared to 2019. Of patients in care in 2019, 11.8% interrupted HIV care in 2020 compared to 9.1% yearly in the 3 previous years. The number of HIV patients with VL monitoring per month dropped in March-May 2020, whilst proportions of VL suppression and ART coverage remained above 86% and 98.5% respectively in 2020. PrEP purchases, number of purchasers and starters dropped during April-May 2020 (respectively - 45.7%, - 47.4%, - 77.9% in April compared to February 2020). CONCLUSIONS: The significant decrease in HIV diagnoses in Belgium in 2020 coincided with the COVID-19 pandemic and following containment measures, particularly in April-May during the first lockdown. A slowdown of HIV transmission due to reduced HIV risk exposure is suggested by the halving in diagnosis of acute HIV infections in March-December 2020 compared to the previous year, and the adaptive decrease in PrEP use and PrEP initiation from April onwards. Despite a slight increase in HIV care interruptions, the indicators of quality of HIV care remained stable. Access to prevention, testing and care for all people living with HIV and at risk of acquiring HIV is a priority during and after times of pandemic.

Unified European support framework to sustain the HIV cascade of care for people living with HIV including in displaced populations of war-struck Ukraine.

Ukraine is one of the countries in Europe most affected by HIV. The escalation of open war on the European continent has affected HIV care in Ukraine in an unprecedented way. Treating physicians in Europe have little experience on how to handle HIV-specific care under these circumstances. A framework is urgently needed that both defines and sets out strategies to handle the specific challenges for emergency support for people living with HIV, both those staying in Ukraine and those becoming displaced. The optimal allocation of the few available medical resources, primarily antiretroviral therapy, is necessary to best prevent individual morbidity and achieve population transmission control. Professional HIV networks play a central role to create, optimise, and execute support strategies. Through a rapid literature review we identified the key strategies needed to create a support framework, adapted to Ukraine's HIV epidemiology. We produce a unified support framework aiming to reduce the inevitable impact on Ukraine's HIV care cascade now, and when rebuilding it after the war.

Disseminated histoplasmosis diagnosed by cross-reactivity with the Aspergillus galactomannan antigen in an HIV-positive patient.

Invasive histoplasmosis is the most common AIDS-defining event in endemic regions such as South America. In non-endemic regions, less familiar to the diagnosis, invasive histoplasmosis can be mistakenly diagnosed as miliary tuberculosis leading to a high mortality rate. Here we present the case of an invasive histoplasmosis mistakenly diagnosed as tuberculosis. The diagnosis of histoplasmosis was considered later on, in light of patient's clinical deterioration and positive Aspergillus galactomannan antigens. This case highlights the importance of considering other opportunistic infections when facing a culture-negative miliary tuberculosis without clinical improvement despite anti-tuberculosis therapy. It also draws our attention to the tools available in non-endemic regions that can be helpful in the diagnosis of invasive histoplasmosis.

A public health value-based healthcare paradigm for HIV.

BACKGROUND: HIV patients face considerable acute and chronic healthcare needs and battling the HIV epidemic remains of the utmost importance. By focusing on health outcomes in relation to the cost of care, value-based healthcare (VBHC) proposes a strategy to optimize quality of care and cost-efficiency. Its implementation may provide an answer to the increasing pressure to optimize spending in healthcare while improving patient outcomes. This paper describes a pragmatic value-based healthcare framework for HIV care. METHODS: A value-based HIV healthcare framework was developed during a series of roundtable discussions bringing together 16 clinical stakeholder representatives from the Belgian HIV reference centers and 2 VBHC specialists. Each round of discussions was focused on a central question translating a concept or idea to the next level of practical implementation: 1) how can VBHC principles be translated into value-based HIV care drivers; 2) how can these value-based HIV care divers be translated into value-based care objectives and activities; and 3) how can value-based HIV care objectives and activities be translated into value-based care indicators. Value drivers were linked to concrete objectives and activities using a logical framework approach. Finally, specific, measurable, and acceptable structure, process and outcomes indicators were defined to complement the framework. RESULTS: Our framework identifies 4 core value areas where HIV care would benefit most from improvements: Prevention, improvement of the cascade of care, providing patient-centered HIV care and sustaining a state-of-the-art HIV disease management context. These 4 core value areas were translated into 12 actionable core value objectives. For each objective, example activities were proposed. Indicators are suggested for each level of the framework (outcome indicators for value areas and objectives, process indicators for suggested activities). CONCLUSIONS: This framework approach outlines how to define a patient- and public health centered value-based HIV care paradigm. It proposes how to translate core value drivers to practical objectives and activities and suggests defining indicators that can be used to track and improve the framework's implementation in practice.

Diagnosis and treatment of gonorrhoea: 2019 Belgian National guideline for primary care.

OBJECTIVES: Gonorrhoea continues to be a public health concern in Belgium with pharyngeal and rectal infections increasing in persons with high-risk sexual behaviour. Belgian health care practitioners rely on international guidance when managing gonorrhoea resulting in non-adapted suboptimal care for the Belgian patient. This guideline will rectify this situation. METHODS: This guideline was developed following an evidence-based approach and involving a guideline development group (GDG). Research questions were prioritised by the GDG and researchers conducted a systematic review of the evidence that was assessed using GRADE approach. RESULTS: The guideline offers recommendations for gonorrhoea diagnosis, treatment and management for primary care professionals in Belgium and applies a risk group approach. This approach aims for improved identification of at-risk persons and targeted testing of at-risk groups; it includes behavioural questioning when deciding on diagnostic sampling and provides clear advice on treatment. The guideline defines when to add surveillance testing for antibiotic resistance, and what consists of good follow-up. RESULTS: A concerted application of this guideline by all stakeholders in Belgium may result in improving the diagnosis of infections and eventually addressing the emerging multi-drug resistance.

Diagnosis and treatment of syphilis: 2019 Belgian National guideline for primary care.

OBJECTIVES: In the last 10 years, Belgium and countries of the European Economic Area and other high-income countries observed an increasing trend in syphilis diagnoses. Men who have sex with men (MSM) are the most affected population explained by high rates of unprotected sex, a greater number of sexual partners, and risk compensation as a result of pre-exposure prophylaxis use. The 2019 European Centre for Disease Prevention and Control (ECDC) technical report on syphilis proposed interventions such as enhanced screening of specific populations at risk. This guideline will address these issues. METHODS: We performed a systematic review of the evidence for diagnosing and treating syphilis. RESULTS: Based on the results, recommendations were formulated for primary health care professionals in Belgium. This syphilis guideline addresses prioritised testing, the sample and test for the diagnosis, the treatment of a person with syphilis including syphilis serology follow-up, and partner management. CONCLUSION: The identification and management of patients with syphilis will benefit from the application of this guideline.

Multimodal Imaging in AIDS-Related Ocular Cryptococcosis.

PURPOSE: To report multimodal imaging findings in two cases of AIDS-related cryptococcal chorioretinitis associated with uveitis and vasculitis. METHODS: Findings on clinical examination, color fundus photography, fluorescein and indocyanine green angiographies, and optical coherence tomography. Patients. Both patients were diagnosed with Cryptococcus neoformans meningitis in the setting of untreated HIV infection with CD4+ T cell count < 100/mm3. Ocular manifestations occurred during the course of the antifungal therapy for meningitis. RESULTS: In both cases, fundus showed vitritis. Fluorescein angiography allowed the characterization of vasculitis lesions, and indocyanine green angiography indicated choroidal involvement. In combination with optical coherence tomography, ICG and FA allowed the assessment of treatment response. CONCLUSION: These two cases reveal the potential of C. neoformans to infect almost all ocular structures and the critical role of multimodal imaging in baseline evaluation and in the follow-up of patients.

Model informed dosing of hydroxycholoroquine in COVID-19 patients: Learnings from the recent experience, remaining uncertainties and gaps.

AIMS: In the absence of a commonly agreed dosing protocol based on pharmacokinetic (PK) considerations, the dose and treatment duration for hydroxychloroquine (HCQ) in COVID-19 disease currently vary across national guidelines and clinical study protocols. We have used a model-based approach to explore the relative impact of alternative dosing regimens proposed in different dosing protocols for hydroxychloroquine in COVID-19. METHODS: We compared different PK exposures using Monte Carlo simulations based on a previously published population pharmacokinetic model in patients with rheumatoid arthritis, externally validated using both independent data in lupus erythematous patients and recent data in French COVID-19 patients. Clinical efficacy and safety information from COVID-19 patients treated with HCQ were used to contextualize and assess the actual clinical value of the model predictions. RESULTS: Literature and observed clinical data confirm the variability in clinical responses in COVID-19 when treated with the same fixed doses. Confounding factors were identified that should be taken into account for dose recommendation. For 80% of patients, doses higher than 800 mg day on day 1 followed by 600 mg daily on following days might not be needed for being cured. Limited adverse drug reactions have been reported so far for this dosing regimen, most often confounded by co-medications, comorbidities or underlying COVID-19 disease effects. CONCLUSION: Our results were clear, indicating the unmet need for characterization of target PK exposures to inform HCQ dosing optimization in COVID-19. Dosing optimization for HCQ in COVID-19 is still an unmet need. Efforts in this sense are a prerequisite for best benefit/risk balance.

Single-tablet regimen of emtricitabine/tenofovir disoproxil fumarate plus cobicistat-boosted elvitegravir increase adherence for HIV postexposure prophylaxis in sexual assault victims.

BACKGROUND: Postexposure prophylaxis (PEP) is a recommended public health intervention after a sexual assault to prevent HIV infection. METHODS: We conducted a retrospective case-control study on how use of a single-tablet regimen (STR) of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (Stribild) affected adherence to PEP and attendance of a follow-up visit to the STI clinic compared with those who received a multitablet regimen (MTR). Data from sexual assault victims consulting for PEP were prospectively recorded between January 2011 and December 2017. Data were systematically collected on patient demographics, time of medical contact, source risk factors, type of exposure, attendance to follow-up visit, reported completion of PEP and adherence based on pharmacy records. RESULTS: A total of 422 patients received PEP following a sexual assault, of whom 52% had documented completion of a 28-day PEP regimen and 71% attended a follow-up clinic visit. Patients who received an elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF)-based STR had a similar likelihood of attending their first follow-up visit (OR: 0.97; 95% CI: 0.64 to 1.48, p=0.90) but were more likely to complete the PEP regimen (OR: 1.70; 95% CI: 1.16 to 2.50, p=0.007). After adjusting for confounders, those who were prescribed an STR regimen were more likely to complete the PEP regimen (OR: 1.66, 95% CI: 1.09 to 2.53, p=0.019) than those who were prescribed an MTR such as stavudine/lamivudine/lopinavir/ritonavir or zidovudine/lamivudine/indinavir/ritonavir. CONCLUSIONS: Sexual assault victims who were prescribed an STR based on EVG/COBI/FTC/TDF were more likely to complete PEP than those who were prescribed an MTR.

Implementation of a protocol and staff educational sessions improves the care of survivors of sexual assault.

OBJECTIVE: We previously conducted an audit of the care provided for survivors of sexual violence seen at our emergency department and observed that 90% of them did not receive optimal care. This study analysed whether the implementation of a new protocol and educational sessions for staff increased the proportion of such patients who received optimal medical care. METHODS: A computerized chart detailing a new care protocol was developed specifically for rape survivors. Educational sessions focusing on the use of the new protocol were organized for healthcare providers. We then conducted another audit that reviewed retrospectively the charts of all survivors of sexual violence who were cared for at a public university hospital. MAIN OUTCOME MEASURE: Optimal medical care was defined as including systematic investigations for sexually transmitted diseases, and the provision of prophylactic antibiotics, a pregnancy test, emergency contraception, and psychological and medical follow-up. RESULTS: We analysed the charts of 362 survivors of sexual violence and observed that all of the required procedures were completed for 337 patients (93%) and the required preventive measures were provided to 325 patients (90%). CONCLUSION: After the implementation of the new protocol and educational sessions, the proportion of survivors who received optimal medical care increased from 10% to 90%. Nevertheless, optimal management also implies social, psychological and legal support. We hope that the establishment of specialist sexual assault centres will further improve management.

High uptake of pre-exposure prophylaxis (PrEP) during early roll-out in Belgium: results from surveillance reports.

Background Since 1 June 2017, oral pre-exposure prophylaxis (PrEP) could be prescribed and reimbursed in Belgium as prophylactic medication for people who are at increased risk of HIV acquisition. The aim of this study was to determine the uptake of daily and event-driven PrEP in Belgium during the first 9 months of roll-out. METHODS: Routine aggregated data on the number of reimbursement requests and the number of boxes of Truvada (Gilead Sciences, Cambridge, UK) delivered for PrEP through the Belgian pharmacies were obtained from the National Institute for Health and Disability Insurance. We also collected aggregated data from seven Aids Reference Centres (ARCs) currently providing most of the PrEP care in Belgium. RESULTS: From 1 June 2017 to 28 February 2018, 1352 requests for reimbursement were approved by the National Institute for Health and Disability Insurance. Almost 98% of those who bought at least one box of 30 tablets of emtricitabine 200mg/tenofovir disoproxil fumarate 300mg (FTC/TDF) in a Belgian pharmacy were male, and most (67%) were between 30 and 50 years of age. According to data obtained from ARCs, the proportion of those choosing event-driven PrEP initially ranged between 29% and 73%. CONCLUSIONS: The uptake of PrEP in Belgium since the start of the roll-out in June 2017 has been high, and almost entirely limited to men who have sex with men, of whom 43% initially prefer a non-daily regimen. A better understanding is needed as to why other populations, such as sub-Saharan African migrants, are not accessing PrEP, as well as the development of a more sustainable PrEP delivery model.

Correction to: Biological tests carried out on serum/plasma samples from donors of human body material for transplantation: Belgian experience and practical recommendations.

The article Biological tests carried out on serum/plasma samples from donors of human body material for transplantation: Belgian experience and practical recommendations.

Biological tests carried out on serum/plasma samples from donors of human body material for transplantation: Belgian experience and practical recommendations.

This paper on the biological tests carried out on serum/plasma samples from donors of human body material (HBM) is the result of a project of the working Group of Superior Health Council of Belgium formed with experts in the field of HBM and infectious serology. Indeed, uncertainty about the interpretation of biological test results currently leads to the sometimes unjustified cancelling of planned donations or the rejection of harvested HBM, whilst more sophisticated diagnostic algorithms would still allow the use of organs or HBM that would otherwise have been rejected. NAT tests will not be discussed in this publication. In the first part some general aspects as the need for a formal agreement between the Tissue Establishment l and the laboratory responsible for the biological testing, but also some specifications regarding testing material, the choice of additional biological tests, and some general aspects concerning interpretation and reporting are discussed. In a second part, detailed information and recommendations concerning the interpretation are presented for each of the mandatory tests (human immunodeficiency virus, hepatitis B virus, hepatitis C virus and syphilis) is presented. A number of not mandatory, but regularly used optional serological tests (e.g. for the detection of antibodies to Toxoplasma gondii, Epstein-Barr virus, human T cell leukemia virus and cytomegalovirus) are also extensively discussed. Although the project was meant to provide clarification and recommendations concerning the Belgian legislation, the majority of recommendations are also applicable to testing of donors of tissues and cells in other (European) countries.

Prevalence of Mycoplasma genitalium in men with urethritis in a large public hospital in Brussels, Belgium: An observational, cross-sectional study.

BACKGROUND: Mycoplasma genitalium (MG) is a cause of urethritis. While resistance to azithromycin is increasing, routine detection of MG is not performed in Belgium, where its prevalence is unknown. The aim of this study is to determine prevalence of MG in men with urethritis. METHOD AND FINDINGS: An "in-house" amplification assay detecting MG was performed on urine of men with complaints of urethritis who consulted the emergency unit or the Sexually Transmitted Infection clinic of our public hospital in Brussels. Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) were tested on the same sample. A total of 187 men were tested. Prevalence of MG was 9% (95% Confidence Interval: 5 to 13.2%). CT was detected in 20%, NG in 22% and 56% of samples were negative for these three pathogens. Neither age, ethnic origin, sexual orientation nor HIV infection were associated with MG urethritis. CONCLUSION: M. genitalium was identified in 9% of men with complaints of urethritis indicating that amplification assay detecting MG should be implemented in routine testing for those patients.

Belgian guidelines for non-occupational HIV post-exposure prophylaxis 2017.

We present the updated Belgian guidelines for the use of non-occupational HIV post-exposure prophylaxis (NONOPEP). This document is inspired by UK guidelines 2015, adapted to the Belgian situation and approved by all AIDS reference centers in Belgium. When recommended, NONOPEP should be initiated as soon as possible, preferably within 24 h of exposure but can be offered up to 72 h. The duration of NONOPEP should be 28 days. These current guidelines include epidemiologic estimations, which can be used to calculate the risk of infection after a potential exposure and help to decide whether or not to start prophylaxis. We review which medications to use in the context of the last Belgian NONOPEP convention, provide a checklist for initial assessment, and make recommendations for monitoring individuals receiving NONOPEP.