Uncovering the Contrasts and Connections in PASC: Viral Load and Cytokine Signatures in Acute COVID-19 versus Post-Acute Sequelae of SARS-CoV-2 (PASC).

The recent global COVID-19 pandemic has had a profound and enduring impact, resulting in substantial loss of life. The scientific community has responded unprecedentedly by investigating various aspects of the crisis, particularly focusing on the acute phase of COVID-19. The roles of the viral load, cytokines, and chemokines during the acute phase and in the context of patients who experienced enduring symptoms upon infection, so called Post-Acute Sequelae of COVID-19 or PASC, have been studied extensively.

Dolutegravir/Lamivudine Is Noninferior to Continuing Dolutegravir- and Non-Dolutegravir-Based Triple-Drug Antiretroviral Therapy in Virologically Suppressed People With Human Immunodeficiency Virus: DUALING Prospective Nationwide Matched Cohort Study.

Background: Confirming the efficacy of dolutegravir/lamivudine in clinical practice solidifies recommendations on its use.

Methods: Prospective cohort study (DUALING) in 24 human immunodeficiency virus (HIV) treatment centers in the Netherlands. HIV RNA-suppressed cases were on triple-drug antiretroviral regimens without prior virological failure or resistance and started dolutegravir/lamivudine.

Dynamics of Low-Level Viremia and Immune Activation after Switching to a Darunavir-Based Regimen.

There is an ongoing debate regarding whether low-level viremia (LLV), in particular persistent LLV, during HIV treatment with optimal adherence originates from low-level viral replication, viral production, or both. We performed an observational study in 30 individuals with LLV who switched to a boosted darunavir (DRV)-based therapy. In-depth virological analyses were used to characterize the viral population and the (activity) of the viral reservoir.

Virological Failure After Switch to Long-Acting Cabotegravir and Rilpivirine Injectable Therapy: An In-depth Analysis.

Background: Long-acting (LA) injectable therapy with cabotegravir (CAB) and rilpivirine (RPV) is currently used as maintenance treatment for human immunodeficiency virus type 1, and has a low risk for virological failure (VF). Although the risk is low, the circumstances and impact of VF in the real-world setting merit further evaluation.

Methods: We performed an in-depth clinical, virological, and pharmacokinetic analysis on the reasons behind and the impact of VF during LA CAB/RPV therapy in 5 cases from the Netherlands.

Long term sequelae after SARS-CoV-2 infection in children: a household study.

Background: In children persistent symptoms after SARS-CoV-2 infection have been reported, however, duration and characteristics of symptoms in previously healthy children remain unclear. Therefore this study aimed to evaluate persisting symptoms in children at 6 and 12 months after a SARS-CoV-2 infection.

Methods: In this prospective cohort study households with a confirmed SARS-CoV-2 positive outbreak were matched 1:1 to household controls from SARS-CoV-2 negative outbreaks.

Clinical validation of novel dried blood spot based collecting device using serum separation for measuring SARS-CoV-2 antibodies.

Accurate surveillance of coronavirus disease 2019 (COVID-19) incidence includes large-scale antibody testing of the population. Current testing methods require collection of venous blood samples by a healthcare worker, or dried blood spot (DBS) collection using finger prick, however this might have some logistic and processing limitations. We investigated the performance of the Ser-Col device for detecting severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies using a finger prick: DBS-like collection system that includes a lateral flow paper for serum separation and allows for automated large scale analysis.

High Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Household Transmission Rates Detected by Dense Saliva Sampling.

Background: Understanding the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) household transmission is important for adequate infection control measures in this ongoing pandemic.

Methods: Households were enrolled upon a polymerase chain reaction-confirmed index case between October and December 2020, prior to the coronavirus disease 2019 vaccination program. Saliva samples were obtained by self-sampling at days 1, 3, 5, 7, 10, 14, 21, 28, 35, and 42 from study inclusion.

[Rectal lesions and liver lesions caused by syphilis].

Background: Syphilis is a sexually transmitted disease, caused by the spirochete Treponema Pallidum. Many different manifestations exist, which can complicate diagnosis.

Case: A 36-year-old man with a known HIV infection, presented himself with rectal blood loss and abdominal pain.

QTc Prolongation in COVID-19 Patients Using Chloroquine.

Chloroquine is used in the treatment of patients with COVID-19 infection, although there is no substantial evidence for a beneficial effect. Chloroquine is known to prolong the QRS and QTc interval on the ECG. To assess the effect of chloroquine on QRS and QTc intervals in COVID-19 patients, we included all inpatients treated with chloroquine for COVID-19 in the Spaarne Gasthuis (Haarlem/Hoofddorp, the Netherlands) and had an ECG performed both in the 72 h before and during or at least 48 h after treatment.

The effect of switching protease inhibitors to raltegravir on endothelial function, in HIV-infected patients.

Objective Lipid management is one of the cornerstones of cardiovascular risk reduction. Treatment of HIV infection with protease inhibitors (PIs) may cause dyslipidaemia, whilst the integrase inhibitor raltegravir (RAL) has a relatively favorable effect on plasma lipids. We examined the effect of switching from PIs to RAL on endothelial function, and its effect on immunological and inflammatory parameters.

Maraviroc Intensification Improves Endothelial Function in Abacavir-Treated Patients, an Open-Label Randomized Cross-Over Pilot Study.

Background: The increased risk of abacavir in cardiovascular disease (CVD) in HIV-infected patients is still being debated. Maraviroc, a CCR5 blocker, has been shown to decrease immune activation and monocyte infiltration in atherosclerotic plaques in murine experiments. Therefore, we examined the effect of maraviroc intensification on flow-mediated dilatation (FMD) in abacavir-treated HIV-infected patients and its effect on immunological and inflammatory parameters.

Quantification of naive and memory T-cell turnover during HIV-1 infection.

Background: In HIV infection, the homeostasis of CD4 and CD8 T cells is dramatically disturbed, and several studies have pointed out that T-cell turnover rates are increased. To understand how the CD4 and CD8 T-cell pools are affected, it is important to have quantitative insights into the lifespans of the cells constituting the different T-lymphocyte populations.

Methods: We used long-term in-vivo H2O labeling and mathematical modeling to estimate the average lifespans of naive and memory CD4 and CD8 T cells in untreated (n = 4) and combination antiretroviral therapy-treated (n = 3) HIV-1-infected individuals.

Maraviroc Intensification of cART in Patients with Suboptimal Immunological Recovery: A 48-Week, Placebo-Controlled Randomized Trial.

Objective: The immunomodulatory effects of the CCR5-antagonist maraviroc might be beneficial in patients with a suboptimal immunological response, but results of different cART (combination antiretroviral therapy) intensification studies are conflicting. Therefore, we performed a 48-week placebo-controlled trial to determine the effect of maraviroc intensification on CD4+ T-cell counts and immune activation in these patients.

Design: Double-blind, placebo-controlled, randomized trial.

Diminished impact of ethnicity as a risk factor for chronic kidney disease in the current HIV treatment era.

Background: Chronic kidney disease (CKD) is an important comorbidity during human immunodeficiency virus (HIV) infection. Historically, HIV-associated nephropathy has been the predominant cause of CKD and has primarily been observed in people of African ancestry. This study aims to investigate the role of ethnicity in relation to CKD risk in recent years.

Maraviroc treatment in non-R5-HIV-1-infected patients results in the selection of extreme CXCR4-using variants with limited effect on the total viral setpoint.

Objectives: Using deep sequencing methods, we intensively investigated the selective pressure of maraviroc on the viral population in four patients with dual/mixed HIV-1 experiencing treatment failure.

Methods: Patients received maraviroc add-on therapy (n = 4). Tropism was determined by Monogram's Trofile assay and/or 'deep' sequencing.

Lower incidence of Pneumocystis jirovecii pneumonia among Africans in the Netherlands host or environmental factors?

Background And Objective: HIV-associated Pneumocystis jirovecii pneumonia (PJP) remains one of the commonest opportunistic infections in Western countries. Although it has been suggested that racial differences in PJP incidence exist, early studies report conflicting results. This study aimed to investigate differences in PJP incidence in a developed country among patients originating from sub-Saharan Africa compared with other regions of origin.

The MOTIVATE trials: maraviroc therapy in antiretroviral treatment-experienced HIV-1-infected patients.

Although the use of combination antiretroviral therapy has resulted in spectacular improvements in morbidity and mortality of HIV-1 infected patients, a need for the development of antiretroviral compounds with new mechanisms of action remains. Maraviroc (Celsentri(®); ViiV Healthcare, Middlesex, UK) is the only drug of the class of chemokine (C-C motif) receptor 5 antagonists registered for treatment for HIV-1-infected antiretroviral therapy-experienced patients. Registration was based on the MOTIVATE-1 and -2 studies, which compared the efficacy and tolerability of maraviroc in combination with optimized background therapy with placebo.

Maraviroc is able to inhibit dual-R5 viruses in a dual/mixed HIV-1-infected patient.

Objectives: Maraviroc is the first licensed chemokine co-receptor 5 (CCR5) co-receptor antagonist in clinical practice. It is currently being used in patients harbouring exclusively CCR5-tropic virus. The objective of the study was to investigate the impact of maraviroc on viruses with different co-receptor preferences in a patient with a dual/mixed (D/M) infection.

Mutation Q95K enhances N155H-mediated integrase inhibitor resistance and improves viral replication capacity.

Objectives: The genetic barrier to development of raltegravir resistance is considered to be low, requiring at least one primary integrase mutation: Y143C, Q148H/K/R or N155H to confer raltegravir therapy failure. However, during continued raltegravir treatment failure, additional mutations may be selected. In a patient failing raltegravir therapy, we investigated the impact of multiple integrase mutations on resistance and viral replication.