The social patterning of Covid-19 vaccine uptake in older adults: A register-based cross-sectional study in Sweden.

BACKGROUND: A broad vaccination coverage is crucial for preventing the spread of Covid-19 and reduce serious illness or death. The aim of this study was to examine social inequalities in Covid-19 vaccination uptake as of 17th May 2021 among Swedish adults aged ≥ 60 years. METHODS: The study population comprised a general population cohort aged 60 years or older (n = 350,805), representative of the Swedish population. Data were collected through the nationwide linked multi-register observational study SCIFI-PEARL, and associations between sociodemographic determinants and Covid-19 vaccination uptake were analysed using logistic regression. Intersectional analyses of sociodemographic heterogeneity were performed by taking several overlapping social dimensions into account. Data availability extended to 17 May 2021. FINDINGS: The overall vaccination coverage was 87·2% by 17th May 2021. Younger age, male sex, lower income, living alone, and being born outside Sweden, were all associated with a lower uptake of vaccination. The lowest Covid-19 vaccination uptake was seen in individuals born in low-or middle-income countries, of which only 60% had received vaccination, with an odds ratio (OR) of not being vaccinated of 6·05 (95% CI: 5·85-6·26) compared to individuals born in Sweden. These associations persisted after adjustments for possible confounding factors. The intersectional analyses showed even larger variations in vaccination in cross-classified sociodemographic subgroups (ranging from 44% to 97%) with marked differences in uptake of vaccination within sociodemographic groups. INTERPRETATION: The uptake of Covid-19 vaccine during the spring of 2021 in Sweden varied substantially both between and within sociodemographic groups. The use of an intersectional approach, taking several overlapping social dimensions into account at the same time rather than only using one-dimensional measures, contributes to a better understanding of the complexity in the uptake of vaccination. FUNDING: SciLifeLab / Knut & Alice Wallenberg Foundation, Swedish Research Council, Swedish government ALF-agreement, FORMAS.

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. METHODS: PBMCs, plasma and CSF were collected from 11 HIV-1-positive individuals at four different timepoints during ATI (NCT02641756). Total and integrated HIV-1 DNA, cell-associated (CA) HIV-1 RNA transcripts and restriction factor (RF) expression were measured by PCR-based assays. Markers of neuroinflammation and neuronal injury [neurofilament light chain (NFL) and YKL-40 protein] were measured in CSF. Additionally, neopterin, tryptophan and kynurenine were measured, both in plasma and CSF, as markers of immune activation. RESULTS: Total HIV-1 DNA, integrated HIV-1 DNA and CA viral RNA transcripts did not differ pre- and post-ATI. Similarly, no significant NFL or YKL-40 increases in CSF were observed between baseline and viral rebound. Furthermore, markers of immune activation did not increase during ATI. Interestingly, the RFs SLFN11 and APOBEC3G increased after ATI before viral rebound. Similarly, Tat-Rev transcripts were increased preceding viral rebound after interruption. CONCLUSIONS: ATI did not increase viral reservoir size and it did not reveal signs of increased neuronal injury or inflammation, suggesting that these well-monitored ATIs are safe. Elevation of Tat-Rev transcription and induced expression of the RFs SLFN11 and APOBEC3G after ATI, prior to viral rebound, indicates that these factors could be used as potential biomarkers predicting viral rebound.

Neurofilament light chain protein as a marker of neuronal injury: review of its use in HIV-1 infection and reference values for HIV-negative controls.

INTRODUCTION: Several CSF biomarkers of neuronal injury have been studied in people living with HIV. At this time, the most useful is the light subunit of the neurofilament protein (NFL). This major structural component of myelinated axons is essential to maintain axonal caliber and to facilitate effective nerve conduction. CSF concentrations of NFL provide a sensitive marker of CNS injury in a number of neurological diseases, including HIV-related neuronal injury. Areas Covered: In this review, the authors describe CSF NFL concentrations across the spectrum of HIV-infection, from its early acute phase to severe immunosuppression, with and without neurological conditions, and with and without antiretroviral treatment (n = 516). Furthermore, in order to provide more precise estimates of age-related upper limits of CSF NFL concentrations, the authors present data from a large number (n = 359) of HIV-negative controls. Expert Commentary: Recently a new ultrasensitive diagnostic assay for quantification of NFL in plasma has been developed, providing a convenient way to assess neuronal damage without having to perform a lumbar puncture. This review also considers our current knowledge of plasma NFL in HIV CNS infection.

External validation of the bilirubin-atazanavir nomogram for assessment of atazanavir plasma exposure in HIV-1-infected patients.

Atazanavir increases plasma bilirubin levels in a concentration-dependent manner. Due to less costly and readily available assays, bilirubin has been proposed as a marker of atazanavir exposure. In this work, a previously developed nomogram for detection of suboptimal atazanavir exposure is validated against external patient populations. The bilirubin nomogram was validated against 311 matching bilirubin and atazanavir samples from 166 HIV-1-infected Norwegian, French, and Italian patients on a ritonavir-boosted regimen. In addition, the nomogram was evaluated in 56 Italian patients on an unboosted regimen. The predictive properties of the nomogram were validated against observed atazanavir plasma concentrations. The use of the nomogram to detect non-adherence was also investigated by simulation. The bilirubin nomogram predicted suboptimal exposure in the patient populations on a ritonavir-boosted regimen with a negative predictive value of 97% (95% CI 95-100). The bilirubin nomogram and monitoring of atazanavir concentrations had similar predictive properties for detecting non-adherence based on simulations. Although both methods performed adequately during a period of non-adherence, they had lower predictive power to detect past non-adherence episodes. Using the bilirubin nomogram for detection of suboptimal atazanavir exposure in patients on a ritonavir-boosted regimen is a rapid and cost-effective alternative to routine measurements of the actual atazanavir exposure in plasma. Its application may be useful in clinical settings if atazanavir concentrations are not available.

Medical resource utilization and cost of HIV-related care in the highly active antiretroviral therapy era at a University Clinic in Sweden.

INTRODUCTION: Little is known regarding healthcare costs for HIV/AIDS patients in the era of highly active antiretroviral therapy (HAART) and subgroups of patients according to the severity and progression of HIV infection in Sweden. The objective of this study is therefore to describe the direct medical resource use and cost of healthcare for HIV patients at a university clinic in Sweden. METHODS: A patient registry database for HIV treatment at the Department of Infectious Diseases, Sahlgrenska University Hospital, between 2000 and 2005 provided information on patient characteristics, antiretroviral drugs and dosages, tests and diagnostic procedures, outpatient visits and inpatient stays. The review used publicly available unit costs with a county council perspective, expressed in 2006 Euros. RESULTS: Two hundred and eighty-five patients with a mean age of 38 years in 2000 (64% men) were followed for 1368 patient-years. They had a mean (median) of 6.3 (0) inpatient days, 4.1 (3.7) physician visits, 4.2 (3.8) nurse visits, 2.6 (0.7) counsellor visits and 11.5 (7.7) tests and diagnostic procedures per patient-year. Only 12 deaths were recorded during the study period, and the proportion of treated patients with successful treatment (HIV-RNA < 50 copies/mL) increased from 74% to 92% during the period. The mean cost per patient-month amounted to €1069. The main cost driver was HIV drugs (51%), followed by inpatient stays (including hospitalizations for opportunistic infections; 22%), outpatient physician, nurse or therapist visits (19%) and diagnostics and tests (7%). All non-drug costs increased with a decreasing CD4 cell count. CONCLUSIONS: Overall, approximately half of the direct costs of HIV treatment were not related to antiretroviral treatment. The non-antiretroviral costs were inversely correlated with HIV-induced immune deficiency.