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.

Transmission of SARS-CoV-2 After COVID-19 Screening and Mitigation Measures for Primary School Children Attending School in Liège, Belgium.

Importance: Recent data suggest a relatively low incidence of COVID-19 among children. The possible role that children attending primary school may play in the transmission of SARS-CoV-2 remains poorly understood. Objective: To gain a better understanding of the possible role of children in the transmission of SARS-CoV-2. Design, Setting, and Participants: This prospective cohort study was conducted from September 21 to December 31, 2020, in a primary school in Liège, Belgium, among a volunteer sample of 181 children, parents, and school employees. Exposures: Participants were tested for SARS-CoV-2 infection once a week for 15 weeks through throat washing, performed with 5 mL of saline and collected in a sterile tube after approximately 30 seconds of gargling. Quantitative reverse transcription-polymerase chain reaction was performed to detect SARS-CoV-2 infection. Main Outcomes and Measures: In case of test positivity, participants were asked to complete a questionnaire aimed at determining the timing of symptom onset and symptom duration. SARS-CoV-2 genetic sequencing was also performed. Confirmed cases were linked based on available information on known contacts and viral sequences. Results: A total of 181 individuals participated in this study, including 63 children (34 girls [54.0%]; mean [SD] age, 8.6 [1.9] years [range, 5-13 years]) and 118 adults (75 women [63.6%]; mean [SD] age, 42.5 [5.7] years [range, 30-59 years]). Forty-five individuals (24.9%) tested positive: 13 children (20.6%; 95% CI, 10.6%-30.6%) and 32 adults (27.1%; 95% CI, 19.1%-35.7%) (P = .34). Children were more often asymptomatic compared with adults (6 [46.2%; 95% CI, 19.1%-73.3%] vs 4 of 31 [12.9%; 95% CI, 1.3%-24.5%]; P = .04). The median duration of symptoms was shorter in children than in adults (0.00 days [IQR, 0.00-1.00 days] vs 15.00 days [IQR, 7.00-22.00 days]). A reconstruction of the outbreak revealed that most transmission events occurred between teachers and between children within the school. Of the observed household transmission events, most seemed to have originated from a child or teacher who acquired the infection at school. Conclusions and Relevance: Despite the implementation of several mitigation measures, the incidence of COVID-19 among children attending primary school in this study was comparable to that observed among teachers and parents. Transmission tree reconstruction suggests that most transmission events originated from within the school. Additional measures should be considered to reduce the transmission of SARS-CoV-2 at school, including intensified testing.

Impact of switch from tenofovir disoproxil fumarate-based regimens to tenofovir alafenamide-based regimens on lipid profile, weight gain and cardiovascular risk score in people living with HIV.

BACKGROUND: As cardiovascular diseases represent the main cause of non-AIDS related death in people living with HIV (PLWH) with undetectable viral load, we evaluated lipid profile, weight gain and calculated cardiovascular risk change after switching from tenofovir disoproxil fumarate (TDF)-based regimens to tenofovir alafenamide (TAF)-based regimens. METHODS: For this retrospective study, we selected HIV-infected patients with suppressed viral load who fitted in one of the two groups below: First group (TDF/TDF): Patients treated continuously with TDF-based regimens. Second group (TDF/TAF): Patients treated with TDF-regimens during at least 6 months then switched to TAF-regimens while maintaining other drugs unchanged. Available data included date of birth, gender, ethnicity, lymphocyte T CD4+ count, weight, height, blood pressure, current/ex/non-smoker, diabetes mellitus, familial cardiovascular event, lipid profile, duration and nature of antiretroviral therapy. Lipid parameters, weight and calculated cardiovascular risk using 5-year reduced DAD score algorithm [Friis-Møller et al. in Eur J Cardiovasc Prev Rehabil 17:491-501, 2010] were analyzed in each groups. RESULTS: Switching from TDF to TAF resulted in a significant increase in triglycerides levels, total cholesterol and HDL cholesterol. LDL cholesterol and total cholesterol/HDL ratio did not show significant changes. Calculated cardiovascular risk increased after switch from TDF- to TAF-based therapy. CONCLUSIONS: Together with favorable outcomes at the bone and kidney levels, potential negative impact of TAF on lipid profile should be included in the reflection to propose the most appropriate and tailored ARV treatment.

Evolution of Drug Interactions With Antiretroviral Medication in People With HIV.

BACKGROUND: Polypharmacy and drug interactions are important issues for HIV-infected individuals. The number and nature of those interactions are continuously evolving with the use of new antiretroviral drugs and the aging of HIV-infected individuals. We aimed to analyze this evolution over time. METHODS: This retrospective cohort study was conducted in the University Hospital of Liège (Belgium). Treatments of HIV-infected outpatients attending Liège University Hospital were collected and analyzed in 2012 and 2016. The University of Liverpool HIV drug interactions database was used to determine drug interactions. RESULTS: We included 1038 patients in 2016, of whom 78% had 1 comedication. Polypharmacy was seen in 20% of the cohort. Four percent of the patients presented red flag interactions, and 38% had orange flag interactions. Nonantiretroviral (non-ARV) therapeutic classes involved in drug interactions were mostly cardiovascular and central nervous system drugs. They were followed by hormone drugs and dietary supplements for orange flag interactions. Two factors significantly contributed to both red and orange flag interactions: the number of non-ARV comedications and protease inhibitor-based ARV regimens. The proportion of patients with red or orange flag interactions remained stable from 2012 to 2016. CONCLUSIONS: This study highlights the persistence of an alarming number of contraindicated drug interactions and a high prevalence of potential drug interactions over time. Identification, prevention, and management of drug interactions remain a key priority in HIV care.

Detectability of HIV Residual Viremia despite Therapy Is Highly Associated with Treatment with a Protease Inhibitor-Based Combination Antiretroviral Therapy.

HIV persistence despite therapy contributes to chronic immune activation and inflammation, increasing the risk of aging-associated events in HIV-infected individuals. We sought here to better understand the complex link between clinical and treatment features and HIV persistence despite therapy. A total of 11,045 samples from 1,160 individuals under combination antiretroviral therapy (cART) with an unquantifiable viral load (VL; limit of quantification, 20 copies/ml) were categorized as detectable or undetectable depending on the detection of a PCR signal using a commercially available assay. Generalized estimating equation (GEE) regression was used to model viral load detectability and to assess the determinants of residual viremia (RV; VL detected below 20 copies/ml) despite therapy. A high VL zenith was associated with a higher probability to have a detectable viremia under cART. Conversely, the probability to have a detectable viral load below 20 copies/ml decreased with time under therapy. Of therapy regimens, protease inhibitor (PI)-based cART was associated with a significantly higher probability of detectable RV compared to nonnucleoside transcriptase inhibitor- or integrase inhibitor-based cART. We found that a PI-based treatment regimen is highly associated with an increased frequency of RV, supporting previous evidence suggesting that PI-based cART regimens could favor ongoing viral replication in some individuals.

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.

Factors associated with late presentation for HIV care in a single Belgian reference center: 2006-2017.

Late presentation for HIV care is a major issue and the cause of higher morbidity, mortality and transmission. In this regard, we analyzed the characteristics of patients presenting for care at our center from January 2006 to July 2017 (n = 687). The majority of the studied population was of African origin (54.3%) with heterosexual women representing the main group (n = 292; 42.5%). 44% of the patients were late presenters (LP) (presenting for care with CD4 T cells <350/mm3 or an AIDS defining event) and 24% were late presenters with advanced disease (LP-AD) (presenting for care with CD4 T cells <200/mm3 or an AIDS defining event). A very high risk of being LP and LP-AD was associated with Sub-Saharan origin (OR 3.4 and 2.6 respectively). Other factors independently associated with LP or LP-AD were age (OR 1.3), male gender (OR 2.0 and 1.5 respectively) and heterosexual route of transmission (OR 2.4 and 2.3 respectively). A significant increase in HIV screening without forgetting those groups would contribute to earlier HIV diagnosis, a key element to end the HIV epidemic. To achieve this goal, addressing the specific hurdles to HIV testing in the migrant population is critical.

Louse-borne relapsing fever in a refugee from Somalia arriving in Belgium.

We report a case of louse-borne relapsing fever (LBRF) in a refugee from Somalia who had arrived in Belgium a few days earlier. He complained of myalgia and secondarily presented fever. Blood smears revealed spirochetes later identified as Borrelia recurrentis. LBRF should be considered in countries hosting refugees, particularly those who transit through endemic regions.

[Update in HIV therapy: tenofovir alafenamide]. / Actualité thérapeutique dans le VIH : le ténofovir alafénamide.

Since the first treatments against human immunodeficiency virus (HIV) have appeared in 1987, important progress has been accomplished. Twenty-four molecules are currently available but only some of them are in common use on account of their easy administration or their weak adverse effects. Tenofovir disoproxil fumarate (TDF) is a commonly used nucleoside reverse-transcriptase inhibitor (NRTI) of HIV. However, taking TDF is sometimes associated with renal toxicity and increased bone demineralization. Tenofovir alafenamide (TAF) is a new prodrug of tenofovir (TFV) whose security profile is more interesting as far as renal and bone complications are concerned, due to a much lower serum concentration and a high intracellular concentration.

Depuis l'apparition des premiers traitements contre le virus de l'immunodéficience humaine (VIH) en 1987, d'importantes avancées ont été réalisées. Vingt-quatre molécules sont actuellement disponibles, mais seules certaines d'entre elles sont fréquemment utilisées en raison de leur facilité d'administration et de leurs faibles effets secondaires. Le ténofovir disoproxil fumarate (TDF) est un inhibiteur nucléotidique de la transcriptase inverse (INTI) du VIH couramment utilisé. Cependant, la prise de TDF est parfois associée à une toxicité rénale ainsi qu'à une déminéralisation osseuse accrue. Le ténofovir alafénamide (TAF) est un nouveau promédicament du ténofovir (TFV) au profil de sécurité plus intéressant sur les plans rénal et osseux, en vertu d'une concentration sérique nettement inférieure et d'une haute concentration intracellulaire.