Dengue and chikungunya: future threats for Northern Europe?

Arthropod-borne viral diseases are likely to be affected by the consequences of climate change with an increase in their distribution and intensity. Among these infectious diseases, chikungunya and dengue viruses are two (re)emergent arboviruses transmitted by Aedes species mosquitoes and which have recently demonstrated their capacity for rapid expansion. They most often cause mild diseases, but they can both be associated with complications and severe forms. In Europe, following the establishment of invasive Aedes spp, the first outbreaks of autochtonous dengue and chikungunya have already occurred. Northern Europe is currently relatively spared, but climatic projections show that the conditions are permissive for the establishment of Aedes albopictus (also known as the tiger mosquito) in the coming decades. It is therefore essential to question and improve the means of surveillance in northern Europe, at the dawn of inevitable future epidemics.

IFNα induces CCR5 in CD4+ T cells of HIV patients causing pathogenic elevation.

BACKGROUND: Among people living with HIV, elite controllers (ECs) maintain an undetectable viral load, even without receiving anti-HIV therapy. In non-EC patients, this therapy leads to marked improvement, including in immune parameters, but unlike ECs, non-EC patients still require ongoing treatment and experience co-morbidities. In-depth, comprehensive immune analyses comparing EC and treated non-EC patients may reveal subtle, consistent differences. This comparison could clarify whether elevated circulating interferon-alpha (IFNα) promotes widespread immune cell alterations and persists post-therapy, furthering understanding of why non-EC patients continue to need treatment. METHODS: Levels of IFNα in HIV-infected EC and treated non-EC patients were compared, along with blood immune cell subset distribution and phenotype, and functional capacities in some cases. In addition, we assessed mechanisms potentially associated with IFNα overload. RESULTS: Treatment of non-EC patients results in restoration of IFNα control, followed by marked improvement in distribution numbers, phenotypic profiles of blood immune cells, and functional capacity. These changes still do not lead to EC status, however, and IFNα can induce these changes in normal immune cell counterparts in vitro. Hypothesizing that persistent alterations could arise from inalterable effects of IFNα at infection onset, we verified an IFNα-related mechanism. The protein induces the HIV coreceptor CCR5, boosting HIV infection and reducing the effects of anti-HIV therapies. EC patients may avoid elevated IFNα following on infection with a lower inoculum of HIV or because of some unidentified genetic factor. CONCLUSIONS: Early control of IFNα is essential for better prognosis of HIV-infected patients.

The treatment for HIV, known as antiretroviral therapy (ART), does not cure HIV but enables individuals to live longer, healthier lives. In this study, we compared immune responses between elite controllers (ECs), who control their HIV infection without any treatment, and ART-treated and untreated patients. We demonstrate that IFNα, a small protein crucial in controlling immune system, is excessively produced at the onset of HIV infection and at levels that persist, resulting in poor HIV control without therapy. We show a mechanism for lack of control of HIV by IFNα. While inhibiting HIV, IFNα also simultaneously increases the HIV co-receptor, CCR5, thereby facilitating virus entry into the target cell. This is avoided by ECs which we hypothesize is associated with a lower infectious inoculum of HIV.

Early elevated IFNα is a key mediator of HIV pathogenesis.

BACKGROUND: A complete understanding of the different steps of HIV replication and an effective drug combination have led to modern antiretroviral regimens that block HIV replication for decades, but these therapies are not curative and must be taken for life. "Elite controllers" (ECs) is a term for the 0.5% of HIV-infected persons requiring no antiretroviral therapy, whose status may point the way toward a functional HIV cure. Defining the mechanisms of this control may be key to understanding how to replicate this functional cure in others. METHODS: In ECs and untreated non-EC patients, we compared IFNα serum concentration, distribution of immune cell subsets, and frequency of cell markers associated with immune dysfunction. We also investigated the effect of an elevated dose of IFNα on distinct subsets within dendritic cells, natural killer cells, and CD4+ and CD8 + T cells. RESULTS: Serum IFNα was undetectable in ECs, but all immune cell subsets from untreated non-EC patients were structurally and functionally impaired. We also show that the altered phenotype and function of these cell subsets in non-EC patients can be recapitulated when cells are stimulated in vitro with high-dose IFNα. CONCLUSIONS: Elevated IFNα is a key mediator of HIV pathogenesis.

Currently, HIV infection is not curable, but infected individuals can manage their condition by taking daily doses of antiretroviral therapy. Some individuals, known as elite controllers (ECs), control their infection without antiretroviral treatment, and studying how their immune system responds to HIV exposure could lead to a potential cure for others. Here, we compare immune cell responses between ECs and untreated non-ECs. We find that IFNα, a small protein with an important role in controlling white blood cell activity, is produced in excess in immune cells from non-ECs compared with ECs during early infection. This insight provides an important clue for the future development of a targeted cure for HIV.

Risk Factors for Late HIV Presentation in Patients Treated at a Single Belgian Reference Centre from 2018 to 2022.

A late HIV diagnosis is associated with increased mortality and morbidity, increased healthcare costs and increased onward viral transmission. In this regard, we retrospectively analysed the characteristics of patients who presented for care at our centre from January 2018 to December 2022 to assess the proportion of patients and factors associated with late HIV presentation. We collected data from the Liège University Hospital database, and we used binary logistic regression models to analyse the impact of individuals' characteristics on late presentation. Among 167 participants, 38.3% were late presenters (LPs) (presenting for care with a CD4+ T-cell count < 350 cells/mm3 or after an AIDS-defining event), and 21.6% were late presenters with advanced disease (LPs-AD) (presenting for care with a CD4+ T-cell count < 200 cells/mm3 or after an AIDS-defining event). The risk of being an LPs-AD was increased in older individuals (OR on log-transformed age: 7.5) and individuals of sub-Saharan African origin compared to individuals of Belgian or other origin (ORs of 0.30 and 0.25, respectively). The results of this study suggest that broadening the focus beyond the previously common risk groups is essential to prevent late diagnosis.

Persistent HIV-1 transcription during ART: time to reassess its significance?

PURPOSE OF REVIEW: Despite suppressive antiretroviral therapy (ART), HIV-1 reservoirs persist and reignite viral replication if therapy is interrupted. Persistence of the viral reservoir in people with HIV-1 (PWH) is the main obstacle to an HIV-1 cure. The reservoirs are not transcriptionally silent, and viral transcripts can be detected in most ART-treated individuals. Here, we review the recent progress in the characterization of persistent HIV-1 transcription during ART. RECENT FINDINGS: Evidence from several studies indicates that, although cell-associated unspliced (US) HIV-1 RNA is abundantly expressed in ART-treated PWH, intact full-length US transcripts are rare and most US RNA is derived from defective proviruses. The transcription- and translation-competent defective proviruses, previously considered irrelevant, are increasingly being linked to residual HIV-1 pathogenesis under suppressive ART. Recent data suggest a continuous crosstalk between the residual HIV-1 activity under ART and the immune system. Persistent HIV-1 transcription on ART, despite being mostly derived from defective proviruses, predicts viral rebound upon therapy interruption, suggesting its role as an indicator of the strength of the host antiviral immune response that is shaping the viral rebound. SUMMARY: In light of the recent findings, the significance of persistent HIV-1 transcription during ART for the long-term health of PWH and the cure research should be reassessed.

Sniffing out safety: canine detection and identification of SARS-CoV-2 infection from armpit sweat.

Detection dogs were trained to detect SARS-CoV-2 infection based on armpit sweat odor. Sweat samples were collected using cotton pads under the armpits of negative and positive human patients, confirmed by qPCR, for periods of 15-30 min. Multiple hospitals and organizations throughout Belgium participated in this study. The sweat samples were stored at -20°C prior to being used for training purposes. Six dogs were trained under controlled atmosphere conditions for 2-3 months. After training, a 7-day validation period was conducted to assess the dogs' performances. The detection dogs exhibited an overall sensitivity of 81%, specificity of 98%, and an accuracy of 95%. After validation, training continued for 3 months, during which the dogs' performances remained the same. Gas chromatography/mass spectrometry (GC/MS) analysis revealed a unique sweat scent associated with SARS-CoV-2 positive sweat samples. This scent consisted of a wide variety of volatiles, including breakdown compounds of antiviral fatty acids, skin proteins and neurotransmitters/hormones. An acceptability survey conducted in Belgium demonstrated an overall high acceptability and enthusiasm toward the use of detection dogs for SARS-CoV-2 detection. Compared to qPCR and previous canine studies, the detection dogs have good performances in detecting SARS-CoV-2 infection in humans, using frozen sweat samples from the armpits. As a result, they can be used as an accurate pre-screening tool in various field settings alongside the PCR test.

Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes.

We aimed to analyse whether patients with ischaemic stroke (IS) occurring within eight days after the onset of COVID-19 (IS-COV) are associated with a specific aetiology of IS. We used SUPERGNOVA to identify genome regions that correlate between the IS-COV cohort (73 IS-COV cases vs. 701 population controls) and different aetiological subtypes. Polygenic risk scores (PRSs) for each subtype were generated and tested in the IS-COV cohort using PRSice-2 and PLINK to find genetic associations. Both analyses used the IS-COV cohort and GWAS from MEGASTROKE (67,162 stroke patients vs. 454,450 population controls), GIGASTROKE (110,182 vs. 1,503,898), and the NINDS Stroke Genetics Network (16,851 vs. 32,473). Three genomic regions were associated (p-value < 0.05) with large artery atherosclerosis (LAA) and cardioembolic stroke (CES). We found four loci targeting the genes PITX2 (rs10033464, IS-COV beta = 0.04, p-value = 2.3 × 10-2, se = 0.02), previously associated with CES, HS6ST1 (rs4662630, IS-COV beta = -0.04, p-value = 1.3 × 10-3, se = 0.01), TMEM132E (rs12941838 IS-COV beta = 0.05, p-value = 3.6 × 10-4, se = 0.01), and RFFL (rs797989 IS-COV beta = 0.03, p-value = 1.0 × 10-2, se = 0.01). A statistically significant PRS was observed for LAA. Our results suggest that IS-COV cases are genetically similar to LAA and CES subtypes. Larger cohorts are needed to assess if the genetic factors in IS-COV cases are shared with the general population or specific to viral infection.

Clinical Outcomes of Third-Generation Cephalosporin Definitive Therapy for Bloodstream Infections Due to Enterobacterales with Potential AmpC Induction: A Single-Center Retrospective Study.

The recommended therapy for severe infections caused by AmpC-inducible Enterobacterales (AmpC-E) typically involves cefepime or carbapenems. In an era of emerging resistance to these antimicrobials, we aim to assess the impact of third-generation cephalosporins (3GCs) vs. alternative antibiotics on clinical outcomes in bloodstream infections (BSIs) due to AmpC-E. We retrospectively included hospitalized adult patients with BSIs caused by 3GC-susceptible AmpC-E between 2012 and 2022, comparing the outcomes of 3GC and non-3GC definitive therapies. The primary outcome was overall treatment failure (OTF), encompassing 90-day all-cause mortality, 90-day reinfection, and 90-day readmission. Secondary outcomes comprised components of the OTF, in-hospital all-cause mortality, and length-of-stay. Within a total cohort of 353 patients, OTF occurred in 46.5% and 41.5% in the 3GC- and non-3GC-therapy groups, respectively (p = 0.36). The 3GC-therapy group exhibited a longer length-of-stay (38 vs. 21 days, p = 0.0003) and higher in-hospital mortality (23.3% vs. 13.4%, p = 0.019). However, the 90-day mortality, 90-day reinfection, and 90-day readmission were comparable between the therapy groups. Subgroup analyses involving high-risk AmpC-E and 3GC vs. standard-of-care yielded similar conclusions. Overall, our findings suggest that 3GC definitive therapy may not result in poorer clinical outcomes for the treatment of BSIs caused by AmpC-E.

Cluster Analysis Identifies Distinct Patterns of T-Cell and Humoral Immune Responses Evolution Following a Third Dose of SARS-CoV-2 Vaccine in People Living with HIV.

(1) Background: Many vaccines require higher, additional doses or adjuvants to provide adequate protection for people living with HIV (PLWH). Despite their potential risk of severe coronavirus disease 2019, immunological data remain sparse, and a clear consensus for the best booster strategy is lacking. (2) Methods: Using the data obtained from our previous study assessing prospective T-cell and humoral immune responses before and after administration of a third dose of SARS-CoV-2 vaccine, we assessed the correlations between immune parameters reflecting humoral and cellular immune responses. We further aimed at identifying distinct clusters of patients with similar patterns of immune response evolution to determine how these relate to demographic and clinical factors. (3) Results: Among 80 PLWH and 51 healthcare workers (HCWs) enrolled in the study, cluster analysis identified four distinct patterns of evolution characterised by specific immune patterns and clinical factors. We observed that immune responses appeared to be less robust in cluster A, whose individuals were mostly PLWH who had never been infected with SARS-CoV-2. Cluster C, whose individuals showed a particularly drastic increase in markers of humoral immune response following the third dose of vaccine, was mainly composed of female participants who experienced SARS-CoV-2. Regarding the correlation study, although we observed a strong positive correlation between markers mirroring humoral immune response, markers of T-cell response following vaccination correlated only in a lesser extent with markers of humoral immunity. This suggests that neutralising antibody titers alone are not always a reliable reflection of the magnitude of the whole immune response. (4) Conclusions: Our findings show heterogeneity in immune responses among SARS-CoV-2 vaccinated PLWH. Specific subgroups could therefore benefit from distinct immunization strategies. Prior or breakthrough natural infection enhances the activity of vaccines and must be taken into account for informing global vaccine strategies among PLWH, even those with a viro-immunologically controlled infection.

Virus-Specific T-Cell Therapy for Viral Infections of the Central Nervous System: A Review.

Opportunistic viral infections of the central nervous system represent a significant cause of morbidity and mortality among an increasing number of immunocompromised patients. Since antiviral treatments are usually poorly effective, the prognosis generally relies on the ability to achieve timely immune reconstitution. Hence, strategies aimed at reinvigorating antiviral immune activity have recently emerged. Among these, virus-specific T-cells are increasingly perceived as a principled and valuable tool to treat opportunistic viral infections. Here we briefly discuss how to develop and select virus-specific T-cells, then review their main indications in central nervous system infections, including progressive multifocal leukoencephalopathy, CMV infection, and adenovirus infection. We also discuss their potential interest in the treatment of progressive multiple sclerosis, or EBV-associated central nervous system inflammatory disease. We finish with the key future milestones of this promising treatment strategy.

Reconstruction of SARS-CoV-2 outbreaks in a primary school using epidemiological and genomic data.

Mathematical modelling studies have shown that repetitive screening can be used to mitigate SARS-CoV-2 transmission in primary schools while keeping schools open. However, not much is known about how transmission progresses within schools and whether there is a risk of importation to households. During the academic year 2020-2021, a prospective surveillance study using repetitive screening was conducted in a primary school and associated households in Liège (Belgium). SARS-CoV-2 screening was performed via throat washing either once or twice a week. We used genomic and epidemiological data to reconstruct the observed school outbreaks using two different models. The outbreaker2 model combines information on the generation time and contact patterns with a model of sequence evolution. For comparison we also used SCOTTI, a phylogenetic model based on the structured coalescent. In addition, we performed a simulation study to investigate how the accuracy of estimated positivity rates in a school depends on the proportion of a school that is sampled in a repetitive screening strategy. We found no difference in SARS-CoV-2 positivity between children and adults and children were not more often asymptomatic compared to adults. Both models for outbreak reconstruction revealed that transmission occurred mainly within the school environment. Uncertainty in outbreak reconstruction was lowest when including genomic as well as epidemiological data. We found that observed weekly positivity rates are a good approximation to the true weekly positivity rate, especially in children, even when only 25% of the school population is sampled. These results indicate that, in addition to reducing infections as shown in modelling studies, repetitive screening in school settings can lead to a better understanding of the extent of transmission in schools during a pandemic and importation risk at the community level.

Human Immunodeficiency Virus Viral Load Monitoring and Rate of Virologic Suppression Among Patients Receiving Antiretroviral Therapy in Democratic Republic of the Congo, 2013-2020.

Background: Antiretroviral therapy (ART) expansion and viral load as a treatment monitoring approach have increased the demand for viral load testing. Many hurdles affect the coverage, quality, and use of viral load results. Estimates of viral load monitoring and viral suppression rates are needed to assess the performance of ART programs and improve human immunodeficiency virus (HIV) management outcomes. Methods: People with HIV (PWH) viral load monitoring data were routinely collected in 84 health facilities in Kinshasa, Democratic Republic of the Congo (DRC), between 2013 and 2020. The number of PWH under ART, the number of participants with at least 1 viral load test result, the rate of viral suppression (defined as ≤1000 HIV ribonucleic acid copies per mL), and the mean turnaround time from sample collection to release of viral load test results were collected together with clinical data. Results: A total of 14 057 PWH were included in the analysis. People with HIV were mainly enrolled after the "test and treat" implementation. The patients were followed for a median period of 27 months. The proportion of PWH with at least 1 available viral load largely increased in recent years. The delay from sample collection to release of viral load test results decreased overtime, from 35 days in 2018 to 16 days in 2020. Pregnancy and advanced HIV disease were associated with a lower chance of viral suppression. Conclusions: There has been considerable success in increasing viral load access for all PWH under therapy in DRC. Nevertheless, viral load testing should be intensified with a particular effort to be made in groups at higher risk of viral failure.

[An emerging cause of chronic fatigue and pain : post-COVID-19 condition or long COVID]. / Une cause émergente de fatigue et de douleurs chroniques : l'affection post-COVID-19 ou COVID long.

Some individuals who have been infected with SARS-CoV-2 can experience long-term effects from their infection, known as post-COVID conditions, post-acute sequelae of COVID-19 or long COVID. Different underlying mechanisms can lead to long COVID, none of which are mutually exclusive. Lingering symptoms can persist years after SARS-CoV-2 infection, including fatigue, muscle weakness, tachycardia, dyspnea and various neurological symptoms. The symptomatology is partly similar to that reported by people with chronic fatigue syndrome and other unwell studied long-lasting diseases that may occur after other infections. People who have experienced more severe COVID-19 illness are at higher risk of developing long COVID, although anyone who was infected can experience post-COVID conditions. Importantly, unvaccinated individuals are more likely to develop long COVID. Here we review the current knowledge and discuss key findings regarding the epidemiology and physiopathology of long COVID. We briefly review current diagnostic and treatment options that remain so far largely insufficient.

Certains individus infectés par le SARS-CoV-2 peuvent présenter des symptômes à long terme, évoluant parfois durant plusieurs années. Il est alors question d'affection post-COVID-19 ou COVID long. Les symptômes sont très polymorphes, fluctuants, et comprennent, notamment, une fatigue intense, des douleurs articulaires et musculaires, de la dyspnée, de la tachycardie, ainsi qu'une constellation de plaintes neurologiques. Cette symptomatologie est, en partie, similaire à celle du syndrome de fatigue chronique et est retrouvée également après d'autres types d'infections. Les mécanismes à l'origine du COVID long sont probablement multiples et encore mal connus. Si le COVID long peut toucher tout individu infecté par le SARS-CoV-2, certains groupes sont plus à risque, notamment les personnes non vaccinées ou les individus ayant présenté une infection sévère. Dans cet article, nous résumons les connaissances actuelles et mettons en lumière les découvertes clés quant à l'épidémiologie et aux mécanismes physiopathologiques du COVID long. Nous discutons aussi des critères diagnostiques et des options thérapeutiques qui sont, à ce jour, largement insuffisantes.

IFNα induces CCR5 in CD4+ T-cells, causing its anti- HIV inefficiency and its subsequent pathogenic elevation, partially controlled by anti-HIV therapy.

Like EC, we find that ART-treated patients control serum IFNα concentration and show few immune cell alterations enabling a healthy but fragile medical status. However, treatment interruption leads to elevated IFNα reflecting virus production indicating that like EC, ART does not achieve a virological cure. The immune system becomes overwhelmed by multiple immune cell abnormalities as found in untreated patients. These are chiefly mediated by elevated IFNα inducing signaling checkpoints abnormalities, including PD1, in cytotoxic immune cells. Importantly, during acute infection, elevated IFNα correlated with HIV load and we found that IFNα enhances CCR5, the HIV coreceptor in CD4+ T-cells, impairing its anti-viral response and accounting for the pathogenic vicious cycle: HIV → IFNα ↗ → infected CD4+ T-cells ↗ →HIV ↗. This study opens immunotherapeutic perspectives showing the need to control IFNα in order to convert ART patients into EC.

Early Elevated IFNα Identified as the Key Mediator of HIV Pathogenesis and its low level a Hallmark of Elite Controllers.

Advances in HIV therapy came from understanding its replication. Further progress toward "functional cure" -no therapy needed as found in Elite Controllers (EC)- may come from insights in pathogenesis and avoidance by EC. Here we show that all immune cells from HIV-infected persons are impaired in non-EC, but not in EC. Since HIV infects few cell types, these results suggest an additional mediator of pathogenesis. We identify that mediator as elevated pathogenic IFNα, controlled by EC likely by their preserved potent NK-cells and later by other killer cells. Since the earliest days of infection predict outcome genetic or chance events must be key to EC, and since we found no unique immune parameter at the onset, we suggest a chance infection with a lower HIV inoculum. These results offer an additional approach toward functional cure: a judicious targeting of IFNα for all non-EC patients.

Efficacy, durability, and tolerability of bictegravir/emtricitabine/tenofovir alafenamide for the treatment of HIV in a real-world setting in Belgium.

OBJECTIVES: Our objective was to evaluate the efficacy, durability, and tolerability of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in a real-world setting in Belgium. METHODS: This was a retrospective, multicentre cohort study involving adult treatment-naïve (TN) and treatment-experienced (TE) people living with HIV receiving BIC/FTC/TAF between 1 January 2019 and 30 September 2020. The primary outcome was rate of virological suppression (plasma HIV-1 viral load <50 copies/mL; on-treatment analysis) at weeks 24 and 48. The main secondary outcomes included loss of virological suppression (LVS; two consecutive viral loads of >200 copies/mL after being virologically suppressed) by week 48 and analysis of resistance-associated mutations at time of LVS; tolerability of BIC/FTC/TAF over the 48-week study period; and change in weight and proportion of participants reporting a >10% weight gain at week 48. RESULTS: Overall, 2001 participants were included. Through 48 weeks, overall rate of virological suppression was 93.5%, with similar results observed in the following subgroups: age ≥50 years (92.7%), women (92.8%), Black sub-Saharan African (91%), TN (94%), TE (93.2%), and non-suppressed at baseline (86.6%). LVS was observed in 0.7% (n = 14) of participants, with one participant developing resistance-associated mutations to nucleoside reverse transcriptase inhibitors (184 V) and integrase strand transfer inhibitors (263KR). Of the 131 (6.5%) treatment discontinuations, the most common reason was an adverse event (2.4%), with the most frequent being central nervous system/psychiatric (0.4%) and gastrointestinal (0.4%) toxicity. Median weight gain at week 48 was 2 kg (interquartile range -1 to 5), and a >10% weight increase was observed in 11.6% of participants. CONCLUSION: In this large real-world cohort, BIC/FTC/TAF showed excellent virological efficacy in a diverse population of patients with HIV. Rare occurrence of emergent drug resistance was observed, and treatment was well tolerated.

Systematic Review of the Key Factors Influencing the Indoor Airborne Spread of SARS-CoV-2.

The COVID-19 pandemic due to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been plaguing the world since late 2019/early 2020 and has changed the way we function as a society, halting both economic and social activities worldwide. Classrooms, offices, restaurants, public transport, and other enclosed spaces that typically gather large groups of people indoors, and are considered focal points for the spread of the virus. For society to be able to go "back to normal", it is crucial to keep these places open and functioning. An understanding of the transmission modes occurring in these contexts is essential to set up effective infection control strategies. This understanding was made using a systematic review, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement (PRISMA) 2020 guidelines. We analyze the different parameters influencing airborne transmission indoors, the mathematical models proposed to understand it, and discuss how we can act on these parameters. Methods to judge infection risks through the analysis of the indoor air quality are described. Various mitigation measures are listed, and their efficiency, feasibility, and acceptability are ranked by a panel of experts in the field. Thus, effective ventilation procedures controlled by CO2-monitoring, continued mask wearing, and a strategic control of room occupancy, among other measures, are put forth to enable a safe return to these essential places.

Efficacy, durability, and tolerability of dolutegravir/lamivudine and dolutegravir/rilpivirine for the treatment of HIV in a real-world setting in Belgium.

OBJECTIVES: A paradigm shift from three-drug regimens to two-drug regimens (2DRs) is currently taking place in real-world clinical practice. This study aimed to describe the efficacy, durability, and tolerability of dolutegravir (DTG)/lamivudine (3TC) and DTG/rilpivirine (RPV) in a real-world setting. METHODS: This was a retrospective, observational, multicentre (ten centres in Belgium) study involving adult treatment-naïve and treatment-experienced people living with HIV on DTG/3TC or DTG/RPV between 1 January 2019 and 30 September 2020. The primary endpoint was rate of virological suppression (VS; plasma HIV-1 viral load [VL] <50 copies/ml) using an on-treatment analysis. Main secondary endpoints included the proportion of people that experienced loss of VS (LVS; defined as two consecutive HIV-1 VLs of >200 copies/ml after initially achieving VS) and a resistance analysis at the time of LVS; rate, incidence, and reasons for discontinuation of treatment (stopping treatment or changing any component of the 2DR); and change in weight, along with the proportion of people reporting a >10% weight gain. Ordinal logistic regression analysis examined associations between baseline variables and >10% on-treatment weight gain. RESULTS: Overall, 948 people were included, of whom 734 (77%) were on DTG/3TC and 214 (23%) were on DTG/RPV. Baseline characteristics included 54% aged ≥50 years, 31% female, 31% Black sub-Saharan African, 95% treatment-experienced, and 8% with HIV-1 VL ≥50 copies/ml. Through 48 weeks, the rate of VS for the overall cohort was 98.3% (99.1% with 3TC; 96.2% with RPV). LVS was observed in 0.5% (n = 5) of the overall population (n = 1 [3TC group], n = 4 [RPV group]). There were 40 treatment discontinuations (4.2%, n = 27 [3TC group]; n = 13 [RPV group]), corresponding to an incidence of 4.7 per 100 patient-years. The most common reason for discontinuation was an adverse event (1.4%), with neurotoxicity the most frequent (0.5%). Median on-treatment weight gain at week 48 was 1 kg (interquartile range [IQR] -1-3) overall, 1 kg (IQR -1-3) in the 3TC group, and 2 kg (IQR 0-4) in the RPV group. A >10% weight increase was observed in 6.3% of people. Regression analysis showed that being on a tenofovir disoproxil fumarate-based regimen prior to 2DR initiation was the only variable associated with a >10% increase in weight from baseline (odds ratio 3.48; 95% confidence interval 1.13-10.68; p = 0.038). CONCLUSION: In this real-world analysis, the 2DRs analysed were effective, durable, and safe for those who were treatment-naive and treatment-experienced. A slight increase in weight was associated with these regimens.

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.