Barriers and missed opportunities in PrEP uptake, use and care among men who have sex with men with recent HIV infection in the Netherlands.

Introduction: Oral pre-exposure prophylaxis (PrEP) prevents Human Immunodeficiency Virus (HIV) acquisition. In the Netherlands, PrEP is accessible through the national PrEP program (NPP) or general practitioners (GP). Still, some men who have sex with men (MSM) entering HIV care indicated having PrEP experience prior to diagnosis.

Booster-free anti-retroviral therapy for persons living with HIV and multidrug resistance (B-Free): protocol for a multicentre, multistage, randomised, controlled, non-inferiority trial.

Introduction: Anti-retroviral therapy (ART) simplification strategies are needed for treatment-experienced people with HIV (PWH) and multidrug-resistant viruses. These individuals are commonly treated with boosted ART regimens and are thereby at risk for harmful drug-drug interactions (DDI). In this trial, we aim to assess the efficacy of the combination doravirine, dolutegravir and lamivudine (DOR/DTG/3TC) among people with a history of virological failure who receive boosted ART.

Real-world effectiveness and tolerability of switching to doravirine-based antiretroviral therapy in people with HIV: a nationwide, matched, prospective cohort study.

Background: Currently, real-world data on doravirine are scarce. In a national prospective cohort, we assessed the effectiveness and tolerability of switching to doravirine-based antiretroviral therapy (ART) in people with HIV.

Methods: We did a nationwide, matched, prospective cohort study of people with HIV without previous virological failure and stable for at least 12 months on non-doravirine-containing triple or dual ART switching to doravirine before Sept 1, 2020 (exposed group).

Integrated analysis of viral blips, residual viremia, and associated factors in people with HIV: Results from a retrospective cohort study.

The etiology of viral blips is not yet fully elucidated. One of the hypotheses is that blips reflect variations in residual viremia (RV) near the detectability threshold. In this study, we evaluated whether RV is associated with viral blips and which factors are associated with RV.

No long-term effect of past Pneumocystis jirovecii pneumonia on pulmonary function in people with HIV.

Objective: To assess the impact of past Pneumocystis jirovecii pneumonia (PJP) on the pulmonary diffusion capacity in people with HIV (PWH) with a history of advanced immunodeficiency.

Design: Prospective cross-sectional study.

Methods: Adult PWH with past PJP >1 year ago were included as the study group.

Long-Term Virological Treatment Outcomes in Adolescents and Young Adults With Perinatally and Non-Perinatally Acquired Human Immunodeficiency Virus.

Background: Long-term viral suppression on antiretroviral therapy (ART) is not established among all people with human immunodeficiency virus (PWH). Young adults (18-24 years) are recognized as a group vulnerable for suboptimal virological treatment outcomes. The aim of this study is to evaluate longitudinal virological treatment outcomes and to identify risk factors for virological failure (VF) among young adults with non-perinatally and perinatally acquired human immunodeficiency virus (HIV) in the Netherlands.

Lower Incidence of HIV-1 Blips Observed During Integrase Inhibitor-Based Combination Antiretroviral Therapy.

Background: As the nature of viral blips remains unclear, their occurrence often leads to uncertainty. This study compares blip incidence rates during treatment with different combination antiretroviral therapy anchors.

Setting: Retrospective cohort study in a tertiary hospital.

Decreased All-Cause and Liver-Related Mortality Risk in HIV/Hepatitis B Virus Coinfection Coinciding With the Introduction of Tenofovir-Containing Combination Antiretroviral Therapy.

Background: The development of efficacious combination antiretroviral therapy (cART) has led to a dramatic decrease in mortality in HIV-positive patients. Specific data on the impact in HIV/hepatitis B virus (HBV)-coinfected patients are lacking. In this study, all-cause and cause-specific mortality risks stratified per era of diagnosis are investigated.

Brief Report: Low Sensitivity of the Fracture Risk Assessment Tool in Young HIV-Infected Patients: Time to Revise Our Screening Strategy.

Objectives: The burden of reduced bone mineral density (BMD) is high among HIV-infected patients. As a screening strategy, current guidelines recommend calculating a Fracture Risk Assessment Tool (FRAX) score in patients aged 40-49 years. Patients with a 10-year risk of a major osteoporotic fracture ≥10% should undergo dual-energy x-ray absorptiometry (DXA) to assess BMD.

The use of corticosteroids does not influence CD4 lymphocyte recovery in HIV-infected patients with advanced immunodeficiency.

Corticosteroids inhibit HIV-related immune activation and seem to have a mild favorable effect on immunological recovery in patients with CD4 counts ≥200 cells/mm. Data in patients with advanced immunodeficiency are lacking. We analyzed whether corticosteroids negatively influence the short-term CD4 lymphocyte recovery in patients with CD4 cell counts <200 cells/mm started on combination antiretroviral therapy (cART).

Switching tenofovir disoproxil fumarate to tenofovir alafenamide results in a significant decline in parathyroid hormone levels: uncovering the mechanism of tenofovir disoproxil fumarate-related bone loss?

: An increasing number of patients have been switched from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide because of its improved bone safety profile, although the pathophysiological mechanism is not fully understood. We show that serum parathyroid hormone levels drop significantly after the switch from TDF to tenofovir alafenamide. This observation supports the theories that TDF-related bone loss is parathyroid hormone-driven and that this effect is dose-dependent.

A Review of Non-Alcoholic Fatty Liver Disease in HIV-Infected Patients: The Next Big Thing?

The burden of liver-related morbidity remains high among HIV-infected patients, despite advances in the treatment of HIV and viral hepatitis. Especially, the impact of non-alcoholic fatty liver disease (NAFLD) is significant with a prevalence of up to 50%. The pathogenesis of NAFLD and the reasons for progression to non-alcoholic steatohepatitis (NASH) are still not fully elucidated, but insulin resistance, mitochondrial dysfunction and dyslipidemia seem to be the main drivers.

Impact of Aging, Cytomegalovirus Infection, and Long-Term Treatment for Human Immunodeficiency Virus on CD8 T-Cell Subsets.

Both healthy aging and human immunodeficiency virus (HIV) infection lead to a progressive decline in naive CD8 T-cell numbers and expansion of the CD8 T-cell memory and effector compartments. HIV infection is therefore often considered a condition of premature aging. Total CD8 T-cell numbers of HIV-infected individuals typically stay increased even after long-term (LT) combination antiretroviral treatment (cART), which is associated with an increased risk of non-AIDS morbidity and mortality.

High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients.

Background: In Western countries emergence of human immunodeficiency virus (HIV) drug resistance has tremendously decreased, and transmission of drug resistance has merely stabilized in recent years. However, in many endemic settings with limited resources rates of emerging and transmitted drug resistance are not regularly assessed.

Methods: We performed a survey including all HIV-infected individuals who received resistance testing in 2010-2015 in Aruba, a highly endemic HIV area in the Caribbean.

Genotypic susceptibility score (GSS) and CD4+ T cell recovery in HIV-1 patients with suppressed viral load.

Objectives: HIV drug resistance, measured by the genotypic susceptibility score (GSS), has a deleterious effect on the virological outcome of HIV-1-infected patients. However, it is not known if GSS retains any predictive value for CD4 recovery in patients with suppressed viral load.

Methods: Four hundred and six patients on virological failure (>500 copies/mL) with GSS  : <6 months prior to switch therapy who achieved undetectable plasma viral load (<50 copies/mL) within 1 year, remained undetectable >1 year on an unchanged regimen and had CD4 data available during entire follow-up were included.

Continuous intravenous infusion of enfuvirtide in a patient with a multidrug-resistant HIV strain.

Case description To evaluate whether continuous intravenous (i.v.) administration of enfuvirtide (T20) could be a suitable alternative to subcutaneous (s.

The presence of protective cytotoxic T lymphocytes does not correlate with shorter lifespans of productively infected cells in HIV-1 infection.

Objectives And Design: CD8+ cytotoxic T lymphocytes (CTL) are important in the control of HIV infection. Although CTL are thought to reduce the lifespan of productively infected cells, CD8+ T-cell depletion in simian immunodeficiency virus-infected rhesus-macaques showed no effect on the lifespan of productively infected cells. As CD8+ T-cell responses that successfully delay HIV disease progression occur only in a minority of HIV-infected individuals, we studied the hypothesis that the ability of CTL to reduce the lifespan of productively infected cells is limited to protective CTL responses only.

Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses.

Introduction: Dolutegravir is a second generation integrase inhibitor with a proposed high genetic barrier to resistance. However, in clinical trials, decreased virological response was seen in a subset of patients with prior exposure to raltegravir and multiple integrase resistance mutations.

Methods: We describe two cases of HIV subtype B-infected patients starting dolutegravir after previous failure on a raltegravir-containing regimen with extensive resistance.

Residual viremia is preceding viral blips and persistent low-level viremia in treated HIV-1 patients.

Background: It has been suggested that low-level viremia or blips in HIV-infected patients on antiretroviral treatment are related to assay variation and/or increased sensitivity of new commercial assays. The 50-copy cut-off for virologic failure is, therefore, under debate.

Methods: Treated patients with low-level viremia (persistent viral loads (VL) of 50-1000 copies/mL, group A, N = 16) or a blip (single detectable VL, group B, N = 77) were compared to a control group (consistently suppressed viremia since start therapy (<50 copies/mL), N = 79).

Infection with the frequently transmitted HIV-1 M41L variant has no influence on selection of tenofovir resistance.

Objectives: In ∼10% of newly diagnosed HIV-1 patients, drug-resistant viral variants are detected. In such transmitted HIV-1 variants, the thymidine analogue mutation (TAM) M41L is frequently observed as a single resistance mutation and these viral variants often belong to phylogenetic transmission clusters. The presence of at least three TAMs, in particular patterns with M41L/L210W, impairs the efficacy of the extensively used drug tenofovir.

Evolution and viral characteristics of a long-term circulating resistant HIV-1 strain in a cluster of treatment-naive patients.

Background: Transmitted resistant HIV may revert to wild-type in the absence of drug pressure due to reduced replication capacity (RC). We observed eight therapy-naive patients infected with HIV harbouring four mutations at nucleoside reverse transcriptase inhibitor (NRTI) resistance-related positions: M41L, T69S, L210E and T215S. If partial reverted resistance patterns like these are detected at baseline, concerns for more extensive resistance in the quasispecies often directs selection of first-line combination antiretroviral therapy (cART) towards more complex regimens.