Integrative Assessment of Total and Intact HIV-1 Reservoir by a 5-Region Multiplexed Rainbow DNA Digital PCR Assay.

Background: Persistent latent reservoirs of intact HIV-1 proviruses, capable of rebounding despite suppressive antiretroviral therapy (ART), hinder efforts towards an HIV-1 cure. Hence, assays specifically quantifying intact proviruses are crucial to assess the impact of curative interventions. Two recent assays have been utilized in clinical trials: intact proviral DNA assay (IPDA) and quadruplex quantitative PCR (Q4PCR).

Staging of immuno-virological dynamics during acute HIV infection in a Belgian prospective cohort study.

Background: The events during acute HIV infection (AHI) set the stage for the subsequent course of the disease. Early initiation of antiretroviral therapy (ART) has been associated with favorable immunovirological outcomes, yet the precise impact of ART timing during AHI remains unclear, particularly on lymphoid tissues.

Materials And Methods: The ACS cohort is a prospective cohort study in Belgium, collecting longitudinal clinical data and human bodily material (HBM) from people diagnosed and treated during AHI.

In depth analysis of the HIV reservoir confirms effectiveness and safety of DTG/3TC in a phase 4 randomized controlled switch trial (RUMBA).

Background: Reducing the number of active compounds for lifelong HIV treatment is of interest, especially to reduce potential long-term side effects. So far, available data assessing viral control, support the robustness and safety of 2DR (2-drug regimen) ART compared to 3DR. However, further in-depth investigations of the viral reservoirs are mandatory to guarantee long-term safety of these regimens regarding stable intact HIV-1 DNA copies, HIV-1 RNA transcripts and sustained immunological control.

The impact of analytical treatment interruptions and trial interventions on time to viral re-suppression in people living with HIV restarting ART in cure-related clinical studies: a systematic review and meta-analysis.

Introduction: To assess the effectiveness of novel HIV curative strategies, "cure" trials require periods of closely monitored antiretroviral therapy (ART) analytical treatment interruptions (ATIs). We performed a systematic review and meta-analysis to identify the impact of ATI with or without novel therapeutics in cure-related studies on the time to viral re-suppression following ART restart.

Methods: Medline, Embase and Web of Science databases were searched for human studies involving ATIs from 1 January 2015 till 22 April 2024.

Longitudinal patterns of inflammatory mediators after acute HIV infection correlate to intact and total reservoir.

Background: Despite the beneficial effects of antiretroviral therapy (ART) initiation during acute HIV infection (AHI), residual immune activation remains a hallmark of treated HIV infection.

Methods: Plasma concentrations of 40 mediators were measured longitudinally in 39 early treated participants of a Belgian AHI cohort (HIV+) and in 21 HIV-negative controls (HIV-). We investigated the association of the inflammatory profile with clinical presentation, plasma viral load, immunological parameters, and in-depth characterization of the HIV reservoir.

Longevity of the humoral and cellular responses after SARS-CoV-2 booster vaccinations in immunocompromised patients.

We assessed the humoral and cellular immune responses after two booster mRNA vaccine administrations [BNT162b2 (Pfizer-BioNTech vaccine)] in cohorts of immunocompromised patients (n = 199) and healthy controls (HC) (n = 54). All patients living with HIV (PLWH) and chronic kidney disease (CKD) patients and almost all (98.2%) of the primary immunodeficiency (PID) patients had measurable antibodies 3 and 6 months after administration of the third and fourth vaccine dose, comparable to the HCs.

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.

Efficacy and safety of camostat mesylate in early COVID-19 disease in an ambulatory setting: a randomized placebo-controlled phase II trial.

Objectives: This study aimed to assess the efficacy and safety of 300 mg camostat mesylate three times daily in a fasted state to treat early phase COVID-19 in an ambulatory setting.

Methods: We conducted a phase II randomized controlled trial in symptomatic (maximum 5 days) and asymptomatic patients with confirmed COVID-19 infection. Patients were randomly assigned in a 2:1 ratio to receive either camostat mesylate or a placebo.

Extensive characterization of HIV-1 reservoirs reveals links to plasma viremia before and during analytical treatment interruption.

The HIV-1 reservoir is composed of cells harboring latent proviruses that have the potential to contribute to viremia upon antiretroviral treatment (ART) interruption. While this reservoir is known to be maintained by clonal expansion of infected cells, the contribution of these cell clones to residual viremia and viral rebound remains underexplored. Here, we conducted an extensive analysis on four ART-treated individuals who underwent an analytical treatment interruption (ATI), characterizing the proviral genomes and associated integration sites of large infected clones and phylogenetically linking these to plasma viremia.

Evaluation of Humoral and Cellular Responses in SARS-CoV-2 mRNA Vaccinated Immunocompromised Patients.

Background: Immunocompromised patients are at increased risk of severe COVID-19 and impaired vaccine response. In this observational prospective study, we evaluated immunogenicity of the BNT162b2 mRNA vaccine in cohorts of primary or secondary immunocompromised patients.

Methods: Five clinical groups of immunocompromised patients [primary immunodeficiency (PID) (n=57), people living with HIV (PLWH) (n=27), secondary immunocompromised patients with a broad variety of underlying rheumatologic (n=23) and homogeneous (multiple sclerosis) neurologic (n=53) conditions and chronic kidney disease (CKD) (n=39)] as well as a healthy control group (n=54) were included.

Focal eosinophilic infiltration of the liver, benign or malignant?

Focal eosinophilic infiltration (FEI) of the liver shares imaging characteristics with malignant hepatic lesions but should be suspected when concomitantly observing eosinophilia. While in itself benign, the cause of FEI should be sought and treated.

Robust sequential biophysical fractionation of blood plasma to study variations in the biomolecular landscape of systemically circulating extracellular vesicles across clinical conditions.

Separating extracellular vesicles (EV) from blood plasma is challenging and complicates their biological understanding and biomarker development. In this study, we fractionate blood plasma by combining size-exclusion chromatography (SEC) and OptiPrep density gradient centrifugation to study clinical context-dependent and time-dependent variations in the biomolecular landscape of systemically circulating EV. Using pooled blood plasma samples from breast cancer patients, we first demonstrate the technical repeatability of blood plasma fractionation.

Return to sport and work after medial open wedge high tibial osteotomy : a case series.

Data on return to work and sport following open wedge high tibial osteotomy (HTO) have been underreported. Furthermore, there is no clear consensus in literature about the postoperative alignment goals following HTO. A retrospective case series was performed to evaluate return to sport and work following open wedge HTO.

Motivations, barriers and experiences of participants in an HIV reservoir trial.

Objectives: We aimed to investigate the motives, barriers and experiences of HIV-STAR study participants. The HIV-STAR study was an analytical HIV treatment interruption trial (ATI) aiming to evaluate the origin of viral rebound, conducted in Ghent, Belgium.

Methods: A mixed-method study was performed among 11 participants of the HIV-STAR study.

Benefits of antiretroviral therapy initiation during acute HIV infection.

: In the last decade, there has been increasing scientific and legislative focus on antiretroviral treatment (ART) for all people living with HIV. Especially early ART initiation, preferably during acute HIV infection, has been named as a promising strategy, both for the individual and for the society. This article will review the benefits and possible future applications of immediate ART initiation during acute HIV infection and explore the remaining hurdles towards this strategy.

Rapid viral rebound after analytical treatment interruption in patients with very small HIV reservoir and minimal on-going viral transcription.

Introduction: Viral remission after analytical treatment interruption (ATI), termed post-treatment control, has been described in a small proportion of HIV-positive patients. This phenomenon has been separately associated to both low levels of HIV-1 proviral DNA as well as cell-associated RNA. We investigated whether the combination of both parameters could help predict delayed viral rebound after treatment interruption (TI).

Evaluating predictive markers for viral rebound and safety assessment in blood and lumbar fluid during HIV-1 treatment interruption.

Background: Validated biomarkers to evaluate HIV-1 cure strategies are currently lacking, therefore requiring analytical treatment interruption (ATI) in study participants. Little is known about the safety of ATI and its long-term impact on patient health.

Objectives: ATI safety was assessed and potential biomarkers predicting viral rebound were evaluated.

Tissue is the issue: when a second biopsy reveals the true diagnosis.

We describe the case of a woman with minimal glomerular changes on initial kidney biopsy. On long-term follow-up, the patient developed nephrotic proteinuria and a second kidney biopsy was performed, which revealed focal segmental glomerulosclerosis (FSGS). Findings from electron microscopy (EM) examination suggested a genetic form of FSGS.

HIV Rebound Is Predominantly Fueled by Genetically Identical Viral Expansions from Diverse Reservoirs.

Viral rebound upon stopping combined antiretroviral therapy poses a major barrier toward an HIV cure. Cellular and anatomical sources responsible for reinitiating viral replication remain a subject of ardent debate, despite extensive research efforts. To unravel the source of rebounding viruses, we conducted a large-scale HIV-STAR (HIV-1 sequencing before analytical treatment interruption to identify the anatomically relevant HIV reservoir) clinical trial.

In-depth validation of total HIV-1 DNA assays for quantification of various HIV-1 subtypes.

HIV-1 DNA quantification serves as an important reservoir biomarker in HIV cure trials. However, the high genetic diversity of HIV-1 represented by different subtypes may bring inaccuracy in quantifying HIV-1 DNA and a sensitive and validated assay covering diverse HIV-1 subtypes is lacking. Therefore, we cross-validated total HIV-1 DNA assays described in literature using a three-step comparative analysis.

Protein expression from unintegrated HIV-1 DNA introduces bias in primary in vitro post-integration latency models.

To understand the persistence of latently HIV-1 infected cells in virally suppressed infected patients, a number of in vitro models of HIV latency have been developed. In an attempt to mimic the in vivo situation as closely as possible, several models use primary cells and replication-competent viruses in combination with antiretroviral compounds to prevent ongoing replication. Latency is subsequently measured by HIV RNA and/or protein production after cellular activation.