1. |
- Demir, Ahmet U., et al.
(author)
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Prevalence of sleep disorders in the Turkish adult population epidemiology of sleep study
- 2015
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In: Sleep and Biological Rhythms. - : Springer Science and Business Media LLC. - 1446-9235 .- 1479-8425. ; 13, s. 298-308
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Journal article (peer-reviewed)abstract
- © 2015 Japanese Society of Sleep Research. Sleep disorders constitute an important public health problem. Prevalence of sleep disorders in Turkish adult population was investigated in a nationwide representative sample of 5021 Turkish adults (2598 women and 2423 men, response rate: 91%) by an interviewer-administered questionnaire. Insomnia was defined by the DSM-IV criteria, habitual snoring and risk for sleep-related breathing disorders (SDB) by the Berlin questionnaire, excessive daytime sleepiness (EDS) by the Epworth sleepiness scale score, and restless legs syndrome (RLS) by the complaints according to the International Restless Legs Syndrome Study Group criteria. Mean age of the participants was 40.7 ± 15.1 (range 18 to 90) years. Prevalence rates (men/women) were insomnia 15.3% (10.5%/20.2%; P < 0.001), high probability of SDB 13.7% (11.1%/20.2%; P < 0.001), EDS 5.4% (5.0%/5.7%; P: 0.09), RLS 5.2% (3.0%/7.3%; P < 0.001). Aging and female gender were associated with higher prevalence of sleep disorders except for habitual snoring. Prevalence rates of the sleep disorders among Turkish adults based on the widely used questionnaires were close to the lower end of the previous estimates reported from different parts of the world. These findings would help for the assessment of the health burden of sleep disorders and addressing the risk groups for planning and implementation of health care. Sleep and Biological Rhythms
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2. |
- Andersson, E., et al.
(author)
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High-throughput sequencing reveals a high prevalence of pretreatment HIV-1 drug resistance in Sweden
- 2021
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In: AIDS. - 1473-5571. ; 35:2, s. 227-234
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Journal article (peer-reviewed)abstract
- OBJECTIVES: HIV-1 pretreatment drug resistance (PDR) is a global concern. Our aim was to evaluate high-throughput sequencing (HTS) for HIV-1 resistance testing and describe PDR in Sweden, where 75% of diagnosed individuals are foreign-born. DESIGN: Cross-sectional study. METHODS: Individuals entering HIV-1 care in Sweden 2017 to March 2019 (n=400) were included if a viremic sample was available (n=220). HTS was performed using an in-house assay. Drug resistance mutations (DRMs) (based on Stanford HIV DB vs. 8.7) at levels 1-5%, 5-19% and at least 20% of the viral population were described. Results from HTS and routine Sanger sequencing were compared. RESULTS: HTS was successful in 88% of patients, 92% when viral load was at least 1000copies/ml. DRMs at any level in protease and/or reverse transcriptase were detected in 95 individuals (49%), whereas DRMs at least 20% in 35 (18%) individuals. DRMs at least 20% correlated well to findings in routine Sanger sequencing. Protease/reverse transcriptase (PR/RT) DRMs at least 20% were predicted by treatment exposure; adjusted OR 9.28 (95% CI 2.24-38.43; P=0.002) and origin in Asia; adjusted OR 20.65 (95% CI 1.66-256.24; P=0.02). Nonnucleoside reverse transcriptase inhibitor (NNRTI) DRMs at least 20% were common (16%) and over-represented in individuals originating from sub-Saharan Africa or Asia. Low-level integrase strand transfer inhibitor (INSTI) DRMs less than 20% were detected in 15 individuals (8%) with no association with INSTI exposure. CONCLUSION: Our HTS can efficiently detect PDR and findings of DRMs at least 20% compare well to routine Sanger sequencing. The high prevalence of PDR was because of NNRTI DRMs and associated with migration from areas with emerging PDR. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
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3. |
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4. |
- Anesten, Birgitta, et al.
(author)
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Blood-brain barrier integrity, intrathecal immunoactivation, and neuronal injury in HIV.
- 2016
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In: Neurology, Neuroimmunology & Neuroinflammation. - 2332-7812. ; 3:6
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Journal article (peer-reviewed)abstract
- Although blood-brain barrier (BBB) impairment has been reported in HIV-infected individuals, characterization of this impairment has not been clearly defined.BBB integrity was measured by CSF/plasma albumin ratio in this cross-sectional study of 631 HIV-infected individuals and 71 controls. We also analyzed CSF and blood HIV RNA and neopterin, CSF leukocyte count, and neurofilament light chain protein (NFL) concentrations. The HIV-infected participants included untreated neuroasymptomatic patients, patients with untreated HIV-associated dementia (HAD), and participants on suppressive antiretroviral treatment (ART).The albumin ratio was significantly increased in patients with HAD compared to all other groups. There were no significant differences between untreated neuroasymptomatic participants, treated participants, and controls. BBB integrity, however, correlated significantly with CSF leukocyte count, CSF HIV RNA, serum and CSF neopterin, and age in untreated neuroasymptomatic participants. In a multiple linear regression analysis, age, CSF neopterin, and CSF leukocyte count stood out as independent predictors of albumin ratio. A significant correlation was found between albumin ratio and CSF NFL in untreated neuroasymptomatic patients and in participants on ART. Albumin ratio, age, and CD4 cell count were confirmed as independent predictors of CSF NFL in multivariable analysis.BBB disruption was mainly found in patients with HAD, where BBB damage correlated with CNS immunoactivation. Albumin ratios also correlated with CSF inflammatory markers and NFL in untreated neuroasymptomatic participants. These findings give support to the association among BBB deterioration, intrathecal immunoactivation, and neuronal injury in untreated neuroasymptomatic HIV-infected individuals.
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5. |
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6. |
- Anesten, Birgitta, et al.
(author)
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Effect of antiretroviral treatment on blood-brain barrier integrity in HIV-1 infection.
- 2021
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In: BMC neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 21:1
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Journal article (peer-reviewed)abstract
- Blood-brain barrier (BBB) injury is prevalent in patients with HIV-associated dementia (HAD) and is a frequent feature of HIV encephalitis. Signs of BBB damage are also sometimes found in neuroasymptomatic HIV-infected individuals without antiretroviral therapy (ART). The aim of this study was to investigate the integrity of the BBB before and after initiation of ART in both neuroasymptomatic HIV infection and in patients with HAD.We determined BBB integrity by measuring cerebrospinal fluid (CSF)/plasma albumin ratios in archived CSF samples prior to and after initiation of ART in longitudinally-followed neuroasymptomatic HIV-1-infected individuals and patients with HAD. We also analyzed HIV RNA in blood and CSF, IgG Index, CSF WBC counts, and CSF concentrations of β2-micoglobulin, neopterin, and neurofilament light chain protein (NfL).We included 159 HIV-infected participants; 82 neuroasymptomatic individuals and 77 with HAD. All neuroasymptomatic individuals (82/82), and 10/77 individuals with HAD, were longitudinally followed with a median (interquartile range, IQR) follow-up of 758 (230-1752) days for the neuroasymptomatic individuals, and a median (IQR) follow-up of 241 (50-994) days for the individuals with HAD. Twelve percent (10/82) of the neuroasymptomatic individuals and 80% (8/10) of the longitudinally-followed individuals with HAD had elevated albumin ratios at baseline. At the last follow-up, 9% (7/82) of the neuroasymptomatic individuals and 20% (2/10) of the individuals with HAD had elevated albumin ratios. ART significantly decreased albumin ratios in both neuroasymptomatic individuals and in patients with HAD.These findings indicate that ART improves and possibly normalizes BBB integrity in both neuroasymptomatic HIV-infected individuals and in patients with HAD.
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7. |
- Beck-Friis, Josefine, et al.
(author)
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Increased risk of hepatotoxicity and temporary drug withdrawal during treatment of active tuberculosis in pregnant women.
- 2020
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In: International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. - : Elsevier BV. - 1878-3511. ; 98, s. 138-143
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Journal article (peer-reviewed)abstract
- Few studies have focused on the treatment of tuberculosis (TB) during pregnancy. This study aimed to evaluate the risk of adverse events, particularly liver toxicity, in pregnant women during treatment for active TB.We conducted a retrospective study on pregnant and age-matched non-pregnant women receiving treatment for active TB at four hospitals in Western Sweden between 1992 and 2017.A total of 135 women were included, 40 pregnant and 95 non-pregnant. The frequency of severe hepatotoxicity was 40% in pregnant women and 6% among non-pregnant women (p < 0.001) (odds ratio 9.9; 95% confidence interval 3.5-28.0). Temporary drug withdrawal due to elevated transaminase levels was more frequent for pregnant than non-pregnant women (40% vs 9.5%; p < 0.001) (odds ratio 6.4; 95% confidence interval 2.5-16.2). There was one fatal case of hepatotoxicity in a pregnant woman.Severe hepatotoxicity was significantly more frequent in pregnant women compared to non-pregnant women. Careful monitoring of liver transaminases while receiving TB treatment during pregnancy is mandatory, as well as ensuring adequate measures with adjustment of drug regimen and temporary drug withdrawals when a rise in liver enzymes is noted.
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8. |
- Beck-Friis, Josefine, et al.
(author)
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No difference in biomarkers of ischemic heart injury and heart failure in patients with COVID-19 who received treatment with chloroquine phosphate and those who did not.
- 2021
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 16:8
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Journal article (peer-reviewed)abstract
- Chloroquine was promoted as a COVID-19 therapeutic early in the pandemic. Most countries have since discontinued the use of chloroquine due to lack of evidence of any benefit and the risk of severe adverse events. The primary aim of this study was to examine if administering chloroquine during COVID-19 imposed an increased risk of ischemic heart injury or heart failure.Medical records, laboratory findings, and electrocardiograms of patients with COVID-19 who were treated with 500 mg chloroquine phosphate daily and controls not treated with chloroquine were reviewed retrospectively. Controls were matched in age and severity of disease.We included 20 patients receiving chloroquine (500 mg twice daily) for an average of five days, and 40 controls. The groups were comparable regarding demographics and biochemical analyses including C-reactive protein, thrombocytes, and creatinine. There were no statistically significant differences in cardiac biomarkers or in electrocardiograms. Median troponin T was 10,8 ng/L in the study group and 17.9 ng/L in the control group, whereas median NT-proBNP was 399 ng/L in patients receiving chloroquine and 349 ng/L in the controls.We found no increased risk of ischemic heart injury or heart failure as a result of administering chloroquine. However, the use of chloroquine to treat COVID-19 outside of clinical trials is not recommended, considering the lack of evidence of its effectiveness, as well as the elevated risk of fatal arrythmias.
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10. |
- Calcagno, A., et al.
(author)
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Determinants of darunavir cerebrospinal fluid concentrations: impact of once-daily dosing and pharmacogenetics
- 2012
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In: Aids. - 0269-9370. ; 26:12, s. 1529-1533
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Journal article (peer-reviewed)abstract
- Objectives: To compare cerebrospinal fluid (CSF) darunavir and ritonavir concentrations in patients receiving darunavir/ritonavir 800/100 mg once daily or 600/100 mg twice daily. To determine the influence of single-nucleotide polymorphisms in the genes encoding for blood-brain barrier transporters (ABCB1 3435 C>T, ABCB1 1236 C>T, ABCB1 2677 G>T, SLCO1A2 38 A>G, SLCO1A2 516 A>C, ABCC2-24 G>A) on darunavir and ritonavir penetration into CSF. Design: Comparative pharmacokinetics study in patients. Methods: Plasma and CSF darunavir and ritonavir concentrations (2-26 h after drug intake) were determined by a validated HPLC coupled with mass spectrometry method in adults on darunavir-based combination antiretroviral therapy undergoing a lumbar puncture. Results: HIV-infected patients on once-daily darunavir/ritonavir had significantly lower CSF darunavir trough concentrations and CSF-to-plasma ratios than patients on darunavir/ritonavir twice-daily (10.7 versus 38.2 ng/ml and 0.32 versus 0.90%; P < 0.05). No significant effect of single-nucleotide polymorphisms in the genes encoding for blood-brain barrier transporters was noted apart from slightly higher CSF darunavir penetration in patients carrying OATP1A2 uncommon variants. Conclusions: This is the first study to compare darunavir CSF concentrations in patients taking the once-daily or the twice-daily dosage: our data show that darunavir and ritonavir dosing significantly affects not only CSF concentrations but also the extent of drug penetration into the CSF. Furthermore a minority of patients in the once-daily arm presented very low CSF concentration of potential concern for HIV control in the central nervous system. The relative importance of pharmacogenetics in influencing CSF darunavir pharmacokinetics deserves further clinical investigation. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
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11. |
- Carlander, C., et al.
(author)
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Assessing cervical intraepithelial neoplasia as an indicator disease for HIV in a low endemic setting: a population-based register study
- 2017
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In: Bjog-an International Journal of Obstetrics and Gynaecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 124:11, s. 1680-1687
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Journal article (peer-reviewed)abstract
- Objectives To analyse whether the prevalence of undiagnosed HIV among (1) all women in Sweden and (2) migrant women, diagnosed with cervical intraepithelial neoplasia grade 2 or worse CIN2+ reaches the threshold of 0.1%, which has been suggested to be cost-effective for HIV testing. Design Population-based register study. Setting Counties of Stockholm and Gothenburg, Sweden, 1990-2014. Population All women, born between 1940 and 1990, with at least one cervical cytology or histology registered in the Swedish National Cervical Screening Register (NKCx). Methods Data were collected from the NKCx and the Swedish National HIV register. The proportion of women with undiagnosed HIV among women with CIN2+ compared with women with a normal/mildly abnormal cytology/histology was assessed. Results The proportion of undiagnosed HIV was higher among all women with CIN2+ than among those without CIN2+: 0.06% (95% CI 0.04-0.08) versus 0.04% (95% CI 0.04-0.04); P = 0.017). Among migrant women, the proportion of undiagnosed HIV was higher among those with CIN2+ than among those without [0.30% (95% CI 0.20-0.43) versus 0.08% (95% CI 0.07-0.10); P < 0.001] and exceeded 0.1%, suggesting the cost-effectiveness of HIV testing. Women with undiagnosed HIV at the time of CIN2+ had a significantly lower nadir CD4+ T-cell count, as a measure of immunosuppression, compared with women without CIN2+ before HIV diagnosis ( median nadir CD4, 95 cells/mm(3) versus 210 cells/mm(3); P < 0.01). Conclusions HIV testing should be performed in migrant women with unknown HIV status diagnosed with CIN2+.
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12. |
- Carlander, Christina, et al.
(author)
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Employment by HIV status, mode of HIV transmission and migrant status : a nation-wide population-based study
- 2021
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In: AIDS. - : Wolters Kluwer. - 0269-9370 .- 1473-5571. ; 35:1, s. 115-123
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Journal article (peer-reviewed)abstract
- Objective: To compare employment in people by HIV status, mode of HIV transmission and migrant status.Design: Nation-wide population-based register data from 1996 to 2016.Methods: All people born between 1940 and 2000 (n = 8587 629) were identified from the Swedish Total Population Register and linked to the Swedish National HIV Register (n = 9492) and Longitudinal Integration Database for Health Insurance and Labour Market Studies. Adjusted prevalence ratios (adjPR) of employment were calculated using Poisson regression. Trends in employment were illustrated in scatterplots with overlaid prediction plots.Results: People with HIV were less likely employed than HIV-negative but with decreasing difference over time [adjPR 0.57, 95% confidence interval (CI) 0.54–0.60 in 1996, adjPR 0.84, 95% CI 0.83–0.86 in 2016]. Female migrants with HIV had the highest increase of employment over time and were more likely employed than HIV-negative female migrants by end of follow-up (adjPR 1.12, 95% CI 1.08–1.16). Swedish-born with present/former intravenous drug use had the lowest employment rates. Individuals with undetectable HIV-RNA viral levels showed higher employment rates (adjPR 1.29, 95% CI 1.20–1.38) compared with those with detectable viral levels.Conclusion: Employment in people living with HIV (PLWH) increased over time but remained lower than for HIV-negative people. HIV was not associated with lower employment in migrants by end of follow-up, indicating that HIV is not a barrier for employment among migrants in Sweden. The heterogeneity of PLWH needs to be taken into account in interventions, and future studies, focusing on access to the labour market in PLWH.
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13. |
- Carlander, C., et al.
(author)
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Employment by HIV status, mode of HIV transmission and migrant status: a nation-wide population-based study
- 2021
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In: Aids. - : Ovid Technologies (Wolters Kluwer Health). - 0269-9370 .- 1473-5571. ; 35:1, s. 115-123
-
Journal article (peer-reviewed)abstract
- Objective: To compare employment in people by HIV status, mode of HIV transmission and migrant status. Design: Nation-wide population-based register data from 1996 to 2016. Methods: All people born between 1940 and 2000 (n = 8587 629) were identified from the Swedish Total Population Register and linked to the Swedish National HIV Register (n = 9492) and Longitudinal Integration Database for Health Insurance and Labour Market Studies. Adjusted prevalence ratios (adjPR) of employment were calculated using Poisson regression. Trends in employment were illustrated in scatterplots with overlaid prediction plots. Results: People with HIV were less likely employed than HIV-negative but with decreasing difference over time [adjPR 0.57, 95% confidence interval (CI) 0.54-0.60 in 1996, adjPR 0.84, 95% CI 0.83-0.86 in 2016]. Female migrants with HIV had the highest increase of employment over time and were more likely employed than HIV-negative female migrants by end of follow-up (adjPR 1.12, 95% CI 1.08-1.16). Swedish-born with present/former intravenous drug use had the lowest employment rates. Individuals with undetectable HIV-RNA viral levels showed higher employment rates (adjPR 1.29, 95% CI 1.20-1.38) compared with those with detectable viral levels. Conclusion: Employment in people living with HIV (PLWH) increased over time but remained lower than for HIV-negative people. HIV was not associated with lower employment in migrants by end of follow-up, indicating that HIV is not a barrier for employment among migrants in Sweden. The heterogeneity of PLWH needs to be taken into account in interventions, and future studies, focusing on access to the labour market in PLWH.
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14. |
- Carlander, Christina, et al.
(author)
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HPV Types in Cervical Precancer by HIV Status and Birth Region : A Population-Based Register Study
- 2020
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In: Cancer Epidemiology, Biomarkers and Prevention. - : AMER ASSOC CANCER RESEARCH. - 1055-9965 .- 1538-7755. ; 29:12, s. 2662-2668
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Journal article (peer-reviewed)abstract
- Background: Data are lacking regarding which human papillomavirus (HPV) types cause high-grade cervical neoplasia (CIN2+) in people with HIV in Europe. We assessed which HPV types are associated with CIN2+ in women living in Sweden by HIV status.Methods: The Swedish National HIV Registry, the Swedish Population Registry, and the Swedish National Cervical Screening Registry were linked. CIN2+ tissue blocks of 130 women living with HIV (WLWH) and 234 HIV-negative women, matched for country of birth (1:2), were retrieved from bio-banks and HPV genotyped. Adjusted ORs (adjOR), stratified by country of birth, were calculated using conditional logistic regression. Matching was broken for cross-group comparisons.Results: WLWH with CIN2 were less likely to have HPV16 [14% vs. 40%; adjOR 0.1; 95% confidence interval (CI), 0.04-0.56] than HIV-negative women, but among women with CIN3, there was no difference in HPV16 prevalence by HIV status (adjOR 0.9; 95% CI, 0.51-1.70). WLWH were six times more likely to have HPV35 in CIN3 than HIV-negative women (adjOR 6.2; 95% CI, 1.3-30.4). WLWH from sub-Saharan Africa (SSA) had less 9-valent vaccine types, compared with both HIV-negative women born in Sweden (adjOR 0.1; 95% CI, 0.02-0.44) and WLWH born in Sweden (adjOR 0.1; 95% CI, 0.01-0.73), mostly because of decreased HPV16 and increased HPV35.Conclusions: WLWH from SSA were less likely to be covered by the 9-valent vaccine, mostly due to less HPV16 and more HPV35. Impact: This could have implications for HPV vaccines, currently not including HPV35, and for HPV-screening algorithms in women with origin from SSA.
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15. |
- Carlander, C., et al.
(author)
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HPV Types in Cervical Precancer by HIV Status and Birth Region: A Population-Based Register Study
- 2020
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In: Cancer Epidemiology Biomarkers & Prevention. - 1055-9965. ; 29:12, s. 2662-2668
-
Journal article (peer-reviewed)abstract
- Background: Data are lacking regarding which human papillomavirus (HPV) types cause high-grade cervical neoplasia (CIN2+) in people with HIV in Europe. We assessed which HPV types are associated with CIN2+ in women living in Sweden by HIV status. Methods: The Swedish National HIV Registry, the Swedish Population Registry, and the Swedish National Cervical Screening Registry were linked. CIN2+ tissue blocks of 130 women living with HIV (WLWH) and 234 HIV-negative women, matched for country of birth (1:2), were retrieved from bio-banks and HPV genotyped. Adjusted ORs (adjOR), stratified by country of birth, were calculated using conditional logistic regression. Matching was broken for cross-group comparisons. Results: WLWH with CIN2 were less likely to have HPV16 [14% vs. 40%; adjOR 0.1; 95% confidence interval (CI), 0.04-0.56] than HIV-negative women, but among women with CIN3, there was no difference in HPV16 prevalence by HIV status (adjOR 0.9; 95% CI, 0.51-1.70). WLWH were six times more likely to have HPV35 in CIN3 than HIV-negative women (adjOR 6.2; 95% CI, 1.3-30.4). WLWH from sub-Saharan Africa (SSA) had less 9-valent vaccine types, compared with both HIV-negative women born in Sweden (adjOR 0.1; 95% CI, 0.02-0.44) and WLWH born in Sweden (adjOR 0.1; 95% CI, 0.01-0.73), mostly because of decreased HPV16 and increased HPV35. Conclusions: WLWH from SSA were less likely to be covered by the 9-valent vaccine, mostly due to less HPV16 and more HPV35. Impact: This could have implications for HPV vaccines, currently not including HPV35, and for HPV-screening algorithms in women with origin from SSA.
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16. |
- Carlander, Christina, et al.
(author)
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Suppressive antiretroviral therapy associates with effective treatment of high-grade cervical intraepithelial neoplasia
- 2018
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In: AIDS. - : LIPPINCOTT WILLIAMS & WILKINS. - 0269-9370 .- 1473-5571. ; 32:11, s. 1475-1484
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Journal article (peer-reviewed)abstract
- Objectives: To assess if women living with HIV (WLWH) have poorer outcome after treatment of cervical intraepithelial neoplasia grade 2, grade 3, adenocarcinoma in situ or cervical cancer (CIN2+) than HIV-negative women (HNW) and to identify predictors of CIN2+ treatment failure and recurrence in WLWH. Design: Population-based cohort study with follow-up between 1983 and 2015. Methods: The Swedish National HIV Registry, the Swedish Population Registry and the Swedish National Cervical Screening Registry were linked to identify all women in Stockholm and Gothenburg counties (Sweden) living with HIV and diagnosed with CIN2+ (n = 179) sometime between 1983 and 2014. For each WLWH, two HNW resident in the same counties and matched for country of birth, diagnosed with CIN2+, were chosen as controls. Treatment failure was defined as the presence of CIN2+ at initial follow-up. Recurrence was defined as the presence of CIN1+ subsequent to an initial normal follow-up. Results: WLWH were three times more likely to have treatment failure (odds ratio (OR) 3.7 [95% confidence interval (CI) 2.0-6.8]) and five times more likely to recur (hazard ratio 5.0 [95% CI 2.1-11.6]) than HNW. Suppressive antiretroviral therapy (ART) at time of treatment of CIN2+ was associated with reduced OR of treatment failure (OR 0.3 [95% CI 0.1-0.8]). Immunosuppression (CD4(+) cell count < 200 cells/mu l) associated strongly with treatment failure (OR compared with CD4 (+) cell count >= 500: 8.5 [95% CI 2.3-30.7]). Conclusion: Suppressive ART is associated with effective treatment of CIN2+. Early HIV diagnosis and ART are essential for successful CIN2+ treatment.
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17. |
- Corell, Alba, et al.
(author)
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Intracranial Manifestation of Melioidosis: A Case Report and Long-Term Follow-Up
- 2020
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In: Cureus. - : Cureus, Inc.. - 2168-8184. ; 12:12
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Journal article (peer-reviewed)abstract
- Primary neurological melioidosis is rare with fewer than 50 cases reported world-wide. We report the first documented case of primary neurological melioidosis in Sweden, a 32-year old male who previously lived in Thailand for six years and recently moved to Sweden. He presented with headache, irritability and lack of concentration. Investigation with computerized tomography (CT) and subsequent magnetic resonance imaging (MRI) showed epidural fluid that was interpreted as a chronic epidural hematoma. He underwent surgical evacuation of the epidural collection that was found to be a white collection mixed with pus and bacterial culture results were positive for Burkholderia pseudomallei.
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18. |
- Dinh, Sofia, et al.
(author)
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Extracutaneous Kaposi sarcoma risk remains higher in people with HIV in the post-ART era
- 2023
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In: AIDS (London, England). - 1473-5571. ; 37:13, s. 2041-2048
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To assess Kaposi sarcoma (KS) by HIV-status in Sweden 1983-2017, with particular focus on extracutaneous KS. DESIGN: Population-based study linking the Total Population Registry, the Swedish HIV Registry InfCareHIV, and the Swedish Cancer Registry. METHODS: We included all Swedish residents, born in or outside Sweden between 1940 and 2000 ( n =8 587 829), assessing the annual incidence of KS, adjusted hazard ratios (adjHR), and odds ratios (adjOR) in the pre and postcombination antiretroviral therapy (ART) eras. RESULTS: KS was found in 324 individuals of whom 202 (62%) were people with HIV (PWH). While the incidence of KS decreased in PWH, it remained higher compared to HIV-negative at end of follow-up (28 vs. 0.09 per 100 000 person-years, P <0.001). In the post-ART era, PWH still had an increased risk of both cutaneous [adjHR 616, 95% confidence interval (CI) 410-926] and extracutaneous KS (adjHR 2068, 95% CI 757-5654), compared to HIV-negative individuals, although there were no cases of extracutaneous disease among virally suppressed PWH. In the post-ART era, the relative risk for KS remained higher in men, particularly men who have sex with men, and viral suppression was associated with lower odds of KS (adjOR 0.05, 95% CI 0.03-0.09). CONCLUSIONS: KS remained increased in PWH in the post-ART era, with a particularly high risk for extracutaneous disease compared to HIV-negative individuals. Notably, there were no cases of extracutaneous disease among virally suppressed PWH, suggesting a less aggressive disease in this population. Further studies on KS in virally suppressed PWH are warranted.
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19. |
- Edén, Arvid, 1975, et al.
(author)
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Residual Central Nervous System Immune Activation Is Not Prevented by Antiretroviral Therapy Initiated During Early Chronic HIV Infection
- 2023
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In: Open Forum Infectious Diseases. - : Oxford University Press (OUP). - 2328-8957. ; 10:2
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Journal article (peer-reviewed)abstract
- Background Antiretroviral therapy (ART) initiated during acute infection can potentially impact the central nervous system (CNS) reservoir, but the differential long-term effects of ART initiation during early or late chronic infection are unknown. Methods We included neuroasymptomatic people with human immunodeficiency virus (HIV) with suppressive ART initiated during chronic (>1 year since transmission) HIV with archived cerebrospinal fluid (CSF) and serum samples after 1 and/or >= 3 years of ART from a cohort study. CSF and serum neopterin was measured using a commercial immunoassay (BRAHMS, Germany). Results In total, 185 people with HIV (median, 79 [interquartile range, 55-128] months on ART) were included. A significant inverse correlation was found between CD4(+) T-cell count and CSF neopterin only at baseline (r = -0.28, P = .002), but not after 1 (r = -0.026, P = .8) or >= 3 (r -0.063, P = .5) years of ART. No significant differences were seen in CSF or serum neopterin concentrations between different pretreatment CD4(+) T-cell strata after 1 or >= 3 (median, 6.6) years of ART. Conclusions In people with HIV initiating ART during chronic infection, occurrence of residual CNS immune activation was not correlated with pretreatment immune status, even when treatment was initiated at high CD4(+) T-cell counts, suggesting that the CNS reservoir, once established, is not differentially affected by the timing of ART initiation during chronic infection.
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20. |
- Edén, Arvid, 1975, et al.
(author)
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Viral Antigen and Inflammatory Biomarkers in Cerebrospinal Fluid in Patients With COVID-19 Infection and Neurologic Symptoms Compared With Control Participants Without Infection or Neurologic Symptoms.
- 2022
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In: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 5:5
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Journal article (peer-reviewed)abstract
- Neurologic symptoms are common in COVID-19, but the central nervous system (CNS) pathogenesis is unclear, and viral RNA is rarely detected in cerebrospinal fluid (CSF).To measure viral antigen and inflammatory biomarkers in CSF in relation to neurologic symptoms and disease severity.This cross-sectional study was performed from March 1, 2020, to June 30, 2021, in patients 18 years or older who were admitted to Sahlgrenska University Hospital, Gothenburg, Sweden, with COVID-19. All patients had CSF samples taken because of neurologic symptoms or within a study protocol. Healthy volunteer and prepandemic control groups were included.SARS-CoV-2 infection.Outcomes included CSF SARS-CoV-2 nucleocapsid antigen (N-Ag) using an ultrasensitive antigen capture immunoassay platform and CSF biomarkers of immune activation (neopterin, β2-microglobulin, and cytokines) and neuronal injury (neurofilament light protein [NfL]).Forty-four patients (median [IQR] age, 57 [48-69] years; 30 [68%] male; 26 with moderate COVID-19 and 18 with severe COVID-19 based on the World Health Organization Clinical Progression Scale), 10 healthy controls (median [IQR] age, 58 [54-60] years; 5 [50%] male), and 41 patient controls (COVID negative without evidence of CNS infection) (median [IQR] age, 59 [49-70] years; 19 [46%] male) were included in the study. Twenty-one patients were neuroasymptomatic and 23 were neurosymptomatic (21 with encephalopathy). In 31 of 35 patients for whom data were available (89%), CSF N-Ag was detected; viral RNA test results were negative in all. Nucleocapsid antigen was significantly correlated with CSF neopterin (r=0.38; P=.03) and interferon γ (r=0.42; P=.01). No differences in CSF N-Ag concentrations were found between patient groups. Patients had markedly increased CSF neopterin, β2-microglobulin, interleukin (IL) 2, IL-6, IL-10, and tumor necrosis factor α compared with controls. Neurosymptomatic patients had significantly higher median (IQR) CSF interferon γ (86 [47-172] vs 21 [17-81] fg/mL; P=.03) and had a significantly higher inflammatory biomarker profile using principal component analysis compared with neuroasymptomatic patients (0.54; 95% CI, 0.03-1.05; P=.04). Age-adjusted median (IQR) CSF NfL concentrations were higher in patients compared with controls (960 [673-1307] vs 618 [489-786] ng/L; P=.002). No differences were seen in any CSF biomarkers in moderate compared with severe disease.In this study of Swedish adults with COVID-19 infection and neurologic symptoms, compared with control participants, viral antigen was detectable in CSF and correlated with CNS immune activation. Patients with COVID-19 had signs of neuroaxonal injury, and neurosymptomatic patients had a more marked inflammatory profile that could not be attributed to differences in COVID-19 severity. These results highlight the clinical relevance of neurologic symptoms and suggest that viral components can contribute to CNS immune responses without direct viral invasion.
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21. |
- Elvstam, Olof, et al.
(author)
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Difficult-to-treat HIV in Sweden: a cross-sectional study
- 2024
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In: BMC INFECTIOUS DISEASES. - 1471-2334. ; 24:1
-
Journal article (peer-reviewed)abstract
- BackgroundOur aim was to examine the prevalence and characteristics of difficult-to-treat HIV in the current Swedish HIV cohort and to compare treatment outcomes between people with difficult and non-difficult-to-treat HIV.MethodsIn this cross-sectional analysis of the Swedish HIV cohort, we identified all people with HIV currently in active care in 2023 from the national register InfCareHIV. We defined five categories of difficult-to-treat HIV: 1) advanced resistance, 2) four-drug regimen, 3) salvage therapy, 4) virologic failure within the past 12 months, and 5) >= 2 regimen switches following virologic failure since 2008. People classified as having difficult-to-treat HIV were compared with non-difficult for background characteristics as well as treatment outcomes (viral suppression and self-reported physical and psychological health).ResultsNine percent of the Swedish HIV cohort in 2023 (n = 8531) met at least one criterion for difficult-to-treat HIV. Most of them had >= 2 regimen switches (6%), and the other categories of difficult-to-treat HIV were rare (1-2% of the entire cohort). Compared with non-difficult, people with difficult-to-treat HIV were older, had an earlier first year of positive HIV test and lower CD4 counts, and were more often female. The viral suppression rate among people with difficult-to-treat HIV was 84% compared with 95% for non-difficult (p = 0.001). People with difficult-to-treat HIV reported worse physical (but not psychological) health, and this remained statistically significant after adjustment for age, sex, and transmission group.ConclusionsAlthough 9% of the HIV cohort in Sweden in 2023 were classified as having difficult-to-treat HIV, a large proportion of these were virally suppressed, and challenges such as advanced resistance and need for salvage therapy are rare in the current Swedish cohort.
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22. |
- Elvstam, Olof, et al.
(author)
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Virological failure and all-cause mortality in HIV-positive adults with low-level viremia during antiretroviral treatment
- 2017
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:7
-
Journal article (peer-reviewed)abstract
- Objective Although most HIV-infected individuals achieve undetectable viremia during antiretroviral therapy (ART), a subset have low-level viremia (LLV) of varying duration and magnitude. The impact of LLV on treatment outcomes is unclear. We investigated the association between LLV and virological failure and/or all-cause mortality among Swedish patients receiving ART. HIV-infected patients from two Swedish HIV centers were identified from the nationwide register InfCare HIV. Subjects aged >= 15 years with triple agent ART were included at 12 months after treatment initiation if >= 2 following viral load measurements were available. Patients with 2 consecutive HIV RNA values >= 1000 copies/mL at this time point were excluded. Participants were stratified into four categories depending on viremia profiles: permanently suppressed viremia (<50 copies/mL), LLV 50-199 copies/mL, LLV 200-999 copies/mL and viremia >= 1000 copies/mL. Association between all four viremia categories and all-cause death was calculated using survival analysis with viremia as a time-varying covariate, so that patients could change viremia category during follow-up. Association between the three lower categories and virological failure >= 2 consecutive measurements >= 1000 copies/mL) was calculated in a similar manner. LLV 50-199 copies/mL was recorded in 70/1015 patients (6.9%) and LLV 200-999 copies/mL in 89 (8.8%) during 7812 person-years of follow-up (median 6.5 years). LLV 200-999 copies/mL was associated with virological failure (adjusted hazard ratio 3.14 [95% confidence interval 1.41-7.03, p<0.01]), whereas LLV 50-199 copies/mL was not (1.01 [0.34-4.31, p = 0.99]; median follow-up 4.5 years). LLV 200-999 copies/mL had an adjusted mortality hazard ratio of 2.29 (0.98-5.32, p = 0.05) and LLV 50-199 copies/mL of 2.19 (0.90-5.37, p = 0.09). In this Swedish cohort followed during ART for a median of 4.5 years, LLV 200-999 copies/mL was independently associated with virological failure. Patients with LLV had higher rates of all-cause mortality, although not statistically significant in multivariate analysis.
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23. |
- Eriksen, Jaran, et al.
(author)
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Antiretroviral treatment for HIV infection: Swedish recommendations 2016.
- 2017
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In: Infectious diseases (London, England). - : Informa UK Limited. - 2374-4243 .- 2374-4235. ; 49:1, s. 1-34
-
Journal article (peer-reviewed)abstract
- The Swedish Medical Products Agency and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly published recommendations for the treatment of HIV infection on seven previous occasions (2002, 2003, 2005, 2007, 2009, 2011 and 2014). In February 2016, an expert group under the guidance of RAV once more revised the guidelines. The most important updates in the present guidelines are as follows: Tenofovir alafenamide (TAF) has recently been registered. TAF has several advantages over tenofovir disoproxilfumarate (TDF) and is recommended instead of TDF in most cases. First-line treatment for previously untreated individuals includes dolutegravir, boosted darunavir or efavirenz with either abacavir/lamivudine or tenofovir (TDF/TAF)/emtricitabine. Pre-exposure prophylaxis (PrEP) is recommended for high-risk individuals. As in the case of the previous publication, recommendations are evidence-graded in accordance with the Oxford Centre for Evidence Based Medicine ( http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/ ) ( Table 1 ). This document does not cover treatment of opportunistic infections and tumours. [Table: see text].
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24. |
- Eriksen, J., et al.
(author)
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Antiretroviral treatment for HIV infection: Swedish recommendations 2019
- 2020
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In: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 52:5, s. 295-329
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Journal article (peer-reviewed)abstract
- The Swedish Reference Group for Antiviral Therapy (RAV) published recommendations for the treatment of HIV infection in this journal most recently in 2017. An expert group under the guidance of RAV here provides updated recommendations. The most important updates in the present guidelines are the following: (a) The risk of HIV transmission through condomless sex from individuals with fully suppressed HIV viral load is effectively zero. (b) Pre-exposure prophylaxis (PrEP) is recommended for groups with a high risk of HIV infection. (c) Since the last update, two new substances have been registered: bictegravir and doravirine. (d) Dual treatment may be an alternative in selected patients, using lamivudine + dolutegravir or lamivudine + boosted darunavir/atazanavir. As with previous publications, recommendations are evidence-graded in accordance with the Oxford Centre for Evidence Based Medicine. This document does not cover treatment of opportunistic infections and tumours.
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25. |
- Gisslén, Magnus, 1962, et al.
(author)
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CSF concentrations of soluble TREM2 as a marker of microglial activation in HIV-1 infection
- 2019
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In: Neurology-Neuroimmunology & Neuroinflammation. - : Ovid Technologies (Wolters Kluwer Health). - 2332-7812. ; 6:1
-
Journal article (peer-reviewed)abstract
- Objective To explore changes in CSF sTREM2 concentrations in the evolving course of HIV-1 infection. In this retrospective cross-sectional study, we measured concentrations of the macrophage/ microglial activation marker sTREM2 in CSF samples from 121 HIV-1-infected adults and 11 HIV-negative controls and examined their correlations with other CSF and blood biomarkers of infection, inflammation, and neuronal injury. CSF sTREM2 increased with systemic and CNS HIV-1 disease severity, with the highest levels found in patients with HIV-associated dementia (HAD). In untreated HIV-1-infected patients without an HAD diagnosis, levels of CSF sTREM2 increased with decreasing CD4(+) T-cell counts. CSF concentrations of both sTREM2 and the neuronal injury marker neurofilament light protein (NFL) were significantly associated with age. CSF sTREM2 levels were also independently correlated with CSF NFL. Notably, this association was also observed in HIV-negative controls with normal CSF NFL. HIV-infected patients on suppressive antiretroviral treatment had CSF sTREM2 levels comparable to healthy controls. Elevations in CSF sTREM2 levels, an indicator of macrophage/microglial activation, are a common feature of untreated HIV-1 infection that increases with CD4(+) T-cell loss and reaches highest levels in HAD. The strong and independent association between CSF sTREM2 and CSF NFL suggests a linkage between microglial activation and neuronal injury in HIV-1 infection. CSF sTREM2 has the potential of being a useful biomarker of innate CNS immune activation in different stages of untreated and treated HIV-1 infection.
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26. |
- Hagberg, Lars, et al.
(author)
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IgG and kappa free light chain CSF/serum indices: evaluating intrathecal immunoglobulin production in HIV infection in comparison with multiple sclerosis.
- 2024
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In: Clinical chemistry and laboratory medicine. - 1437-4331.
-
Journal article (peer-reviewed)abstract
- To study intrathecal kappa free light chain (KFLC) synthesis in people living with HIV (PLWH) in comparison with multiple sclerosis (MS).Cross-sectional analysis including 56 untreated and 150 well treated PLWH, and compared with 58 controls, and 223 MS patients.Elevated serum/cerebrospinal fluid (CSF) IgG and KFLC indices were observed in untreated PLWH. Seventy percent of untreated PLWH had KFLC index above 6.1, a threshold associated with clinically isolated syndrome/MS diagnosis. No association was found between KFCL index and CSF markers of neuronal injury in either PLWH or MS patients.HIV-related immune system dysfunction is often associated with an elevated KFLC index akin to those observed in MS. HIV infection should be considered as a differential diagnosis for patients presenting with neurological symptoms and increased intrathecal immunoglobulin synthesis.
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27. |
- Hermansson, Linn, et al.
(author)
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Cerebrospinal fluid levels of glial marker YKL-40 strongly associated with axonal injury in HIV infection
- 2019
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In: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 16:1
-
Journal article (peer-reviewed)abstract
- BackgroundHIV-1 infects the central nervous system (CNS) shortly after transmission. This leads to a chronic intrathecal immune activation. YKL-40, a biomarker that mainly reflects activation of astroglial cells, has not been thoroughly investigated in relation to HIV. The objective of our study was to characterize cerebrospinal fluid (CSF) YKL-40 in chronic HIV infection, with and without antiretroviral treatment (ART).MethodsYKL-40, neopterin, and the axonal marker neurofilament light protein (NFL) were analyzed with ELISA in archived CSF samples from 120 HIV-infected individuals (85 untreated neuroasymptomatic patients, 7 with HIV-associated dementia, and 28 on effective ART) and 39 HIV-negative controls.ResultsCSF YKL-40 was significantly higher in patients with HIV-associated dementia compared to all other groups. It was also higher in untreated neuroasymptomatic individuals with CD4 cell count <350 compared to controls. Significant correlations were found between CSF YKL-40 and age (r=0.38, p<0.001), CD4 (r=-0.36, p<0.001), plasma HIV RNA (r=0.35, p<0.001), CSF HIV RNA (r=0.35, p<0.001), CSF neopterin (r=0.40, p<0.001), albumin ratio (r=0.44, p<0.001), and CSF NFL (r=0.71, p<0.001). Age, CD4 cell count, albumin ratio, and CSF HIV RNA were found as independent predictors of CSF YKL-40 concentrations in multivariable analysis. In addition, CSF YKL-40 was revealed as a strong independent predictor of CSF NFL together with age, CSF neopterin, and CD4 cell count.ConclusionsCSF YKL-40 is a promising biomarker candidate for understanding the pathogenesis of HIV in the CNS. The strong correlation between CSF YKL-40 and NFL suggests a pathogenic association between astroglial activation and axonal injury, and implies its utility in assessing the prognostic value of YKL-40.
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28. |
- Hermansson, Linn, et al.
(author)
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Plasma concentration of neurofilament light chain protein decreases after switching from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate
- 2019
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 14:12
-
Journal article (peer-reviewed)abstract
- Background Because tenofovir alafenamide (TAF) leads to significantly lower plasma tenofovir concentrations than tenofovir disoproxil fumarate (TDF) and is a stronger substrate for P-glycoprotein (P-gp) than TDF, TAF could lead to decreased central nervous system (CNS) tenofovir exposure than TDF. We aimed to determine if switching from TDF to TAF increases the risk of neuronal injury, by quantifying plasma levels of neurofilament light protein (NfL), a sensitive marker of neuronal injury in HIV CNS infection. Methods Plasma NfL concentration was measured at baseline, week 24, and week 84 in stored plasma samples from 416 participants (272 switching to elvitegravir (E)/cobicistat (C)/emtricitabine (F)/TAF and 144 continuing E/C/F/TDF) enrolled in the randomized, active-controlled, multicenter, open-label, noninferiority Gilead GS-US-292-0109 trial. Results While plasma NfL levels in both groups were within the normal range, we found a small but significant decrease in the E/C/F/TAF arm after 84 weeks from a geometric mean of 9.3 to 8.8 pg/mL (5.4% decline, 95% CI 2.0-8.4, p = 0.002). This change was significantly different (p = 0.001) from that of the E/C/F/TDF arm, in which plasma NfL concentration changed from 9.7 pg/mL at baseline to 10.2 pg/mL at week 84 (5.8% increase, 95% CI -0.8-12.9, p = 0.085). This increase is in line with what could be expected in normal ageing. Plasma NfL concentrations significantly correlated with age. No correlation was found between plasma NfL and serum creatinine. Conclusions We found no biomarker evidence of CNS injury when switching from TDF to TAF. It is unclear whether the small decrease in plasma NfL found after switch to TAF is of any clinical relevance, particularly with plasma NfL levels in both arms remaining within the limits found in HIV-negative controls. These results indicate that switching from TDF to TAF appears safe with regard to neuronal injury.
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29. |
- Holmqvist, Jacob, et al.
(author)
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Cardiac dysfunction and mortality in critically ill patients with COVID-19: A Swedish multicentre observational study
- 2022
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 66:5, s. 606-614
-
Journal article (peer-reviewed)abstract
- Background The prevalence and importance of cardiac dysfunction in critically ill patients with COVID-19 in Sweden is not yet established. The aim of the study was to assess the prevalence of cardiac dysfunction and elevated pulmonary artery pressure (PAP), and its influence on mortality in patients with COVID-19 in intensive care in Sweden. Methods This was a multicentre observational study performed in five intensive care units (ICUs) in Sweden. Patients admitted to participating ICU with COVID-19 were examined with echocardiography within 72 h from admission and again after 4 to 7 days. Cardiac dysfunction was defined as left ventricular (LV) dysfunction (ejection fraction <50% and/or regional hypokinesia) or right ventricular (RV) dysfunction (defined as TAPSE <17 mm or visually assessed moderate/severe RV dysfunction). Results We included 132 patients, of whom 127 (96%) were intubated. Cardiac dysfunction was found in 42 (32%) patients. Most patients had cardiac dysfunction at the first assessment (n = 35) while a few developed cardiac dysfunction later (n = 7) and some changed type of dysfunction (n = 3). LV dysfunction was found in 21 and RV dysfunction in 19 patients, while 5 patients had combined dysfunction. Elevated PAP was found in 34 patients (26%) and was more common in patients with RV dysfunction. RV dysfunction and elevated PAP were independently associated with an increased risk of death (OR 3.98, p = .013 and OR 3.88, p = .007, respectively). Conclusions Cardiac dysfunction occurs commonly in critically ill patients with COVID-19 in Sweden. RV dysfunction and elevated PAP are associated with an increased risk of death.
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30. |
- Hu, Zicheng, et al.
(author)
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Changes in Cerebrospinal Fluid Proteins across the Spectrum of Untreated and Treated Chronic HIV-1 Infection.
- 2024
-
In: bioRxiv : the preprint server for biology.
-
Journal article (peer-reviewed)abstract
- Using the Olink Explore 1536 platform, we measured 1,463 unique proteins in 303 cerebrospinal fluid (CSF) specimens from four clinical centers that included uninfected controls and 12 groups of people living with HIV-1 infection representing the spectrum of progressive untreated and treated chronic infection. We present three initial analyses of these measurements: an overview of the CSF protein features of the sample; correlations of the CSF proteins with CSF HIV-1 RNA and neurofilament light chain protein (NfL) concentrations; and comparison of the CSF proteins in HIV-associated dementia ( HAD ) and neurosymptomatic CSF escape ( NSE ). These reveal a complex but coherent picture of CSF protein changes that includes highest concentrations of many proteins during CNS injury in the HAD and NSE groups and variable protein changes across the course of neuroasymptomatic systemic HIV-1 progression, including two common patterns, designated as lymphoid and myeloid patterns, related to the principal involvement of their underlying inflammatory cell lineages. Antiretroviral therapy reduced CSF protein perturbations, though not always to control levels. The dataset of these CSF protein measurements, along with background clinical information, is posted online. Extended studies of this unique dataset will provide more detailed characterization of the dynamic impact of HIV-1 infection on the CSF proteome across the spectrum of HIV-1 infection, and further the mechanistic understanding of HIV-1-related CNS pathobiology.
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31. |
- Kanberg, Nelly, et al.
(author)
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COVID-19 Recovery: Consistent Absence of Cerebrospinal Fluid Biomarker Abnormalities in Patients With Neurocognitive Post-COVID Complications.
- 2024
-
In: The Journal of infectious diseases. - 1537-6613. ; 229:2, s. 493-501
-
Journal article (peer-reviewed)abstract
- To investigate evidence of residual viral infection, intrathecal immune activation, central nervous system (CNS) injury, and humoral responses in cerebrospinal fluid (CSF) and plasma in patients recovering from coronavirus disease 2019 (COVID-19), with or without neurocognitive post-COVID condition (PCC).Thirty-one participants (25 with neurocognitive PCC) underwent clinical examination, lumbar puncture, and venipuncture ≥3 months after COVID-19 symptom onset. Healthy volunteers were included. CSF and plasma severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid and spike antigen (N-Ag, S-Ag), and CSF biomarkers of immune activation and neuronal injury were analyzed.SARS-CoV-2 N-Ag or S-Ag were undetectable in all samples and no participant had pleocytosis. We detected no significant differences in CSF and plasma cytokine concentrations, albumin ratio, IgG index, neopterin, β2M, or in CSF biomarkers of neuronal injury and astrocytic damage. Furthermore, principal component analysis (PCA1) analysis did not indicate any significant differences between the study groups in the marker sets cytokines, neuronal markers, or anti-cytokine autoantibodies.We found no evidence of ongoing viral replication, immune activation, or CNS injury in plasma or CSF in patients with neurocognitive PCC compared with COVID-19 controls or healthy volunteers, suggesting that neurocognitive PCC is a consequence of events suffered during acute COVID-19 rather than persistent viral CNS infection or residual CNS inflammation.
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32. |
- Kanberg, Nelly, et al.
(author)
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Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19.
- 2020
-
In: Neurology. - 1526-632X .- 0028-3878. ; 95:12
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Journal article (peer-reviewed)abstract
- To test the hypothesis that coronavirus disease 2019 (COVID-19) has an impact on the CNS by measuring plasma biomarkers of CNS injury.We recruited 47 patients with mild (n = 20), moderate (n = 9), or severe (n = 18) COVID-19 and measured 2 plasma biomarkers of CNS injury by single molecule array, neurofilament light chain protein (NfL; a marker of intra-axonal neuronal injury) and glial fibrillary acidic protein (GFAp; a marker of astrocytic activation/injury), in samples collected at presentation and again in a subset after a mean of 11.4 days. Cross-sectional results were compared with results from 33 age-matched controls derived from an independent cohort.The patients with severe COVID-19 had higher plasma concentrations of GFAp (p = 0.001) and NfL (p < 0.001) than controls, while GFAp was also increased in patients with moderate disease (p = 0.03). In patients with severe disease, an early peak in plasma GFAp decreased on follow-up (p < 0.01), while NfL showed a sustained increase from first to last follow-up (p < 0.01), perhaps reflecting a sequence of early astrocytic response and more delayed axonal injury.We show neurochemical evidence of neuronal injury and glial activation in patients with moderate and severe COVID-19. Further studies are needed to clarify the frequency and nature of COVID-19-related CNS damage and its relation to both clinically defined CNS events such as hypoxic and ischemic events and mechanisms more closely linked to systemic severe acute respiratory syndrome coronavirus 2 infection and consequent immune activation, as well as to evaluate the clinical utility of monitoring plasma NfL and GFAp in the management of this group of patients.
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33. |
- Krut, Jan Jessen, et al.
(author)
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No support for premature central nervous system aging in HIV-1 when measured by cerebrospinal fluid phosphorylated tau (p-tau).
- 2017
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In: Virulence. - : Informa UK Limited. - 2150-5608 .- 2150-5594. ; 8:5, s. 599-604
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Journal article (peer-reviewed)abstract
- The prevalence of neurocognitive deficits are reported to be high in HIV-1 positive patients, even with suppressive antiretroviral treatment, and it has been suggested that HIV can cause accelerated aging of the brain. In this study we measured phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) as a potential marker for premature central nervous system (CNS) aging. P-tau increases with normal aging but is not affected by HIV-associated neurocognitive disorders.
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34. |
- Malmstrom, Stina, et al.
(author)
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Failure to restore CD4(+) cell count associated with infection-related and noninfection-related cancer
- 2022
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In: AIDS. - : Ovid Technologies (Wolters Kluwer Health). - 0269-9370 .- 1473-5571. ; 36:3, s. 447-457
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Journal article (peer-reviewed)abstract
- Objective: To assess incidence and relative risk of cancer in Sweden, by HIV status, from 1988 to 2017. Design: Population-based register study. Methods: From the Swedish Total Population Register, all people born between 1940 and 2000 (n = 8 587 629), and resident in Sweden sometime 1983-2017 were identified and linked to National HIV Register InfCareHIV, National Cancer Register, and LISA database. We present incidence and adjusted hazard ratios (adjHR) of infection and noninfection-related cancer for three periods between 1988 and 2017. Results: Incidence and relative risk of infection-related cancer decreased but remained higher in people with HIV (PWH) than in HIV-negative. The proportion attributable to infection remained higher in PWH than in HIV-negative (44 vs. 9%). Women with HIV had lower risk of infection-related cancer than men with HIV [adjusted hazard ratio (adjHR) 0.6, 95% CI 0.4-0.9], mainly driven by lower incidence of Kaposi's sarcoma (adjHR 0.1, 95% CI 0.0-0.4). Current viral suppression (adjHR 0.3, 95% CI 0.2-0.5) was associated with lower risk of infection-related cancer. Current CD4(+) cell count less than 200 cells/mu l was associated with both infection-related (adjHR 15.3, 95% CI 10.7-21.8) and noninfection-related cancer (adjHR 2.5, 95% CI 1.5-4.1), as was CD4(+) cell count increases less than 100 cells/mu l post antiretroviral therapy (ART) (infection-related cancer adjHR 6.6, 95% CI 4.2-10.6, noninfection-related cancer adjHR 2.0, 95% CI 1.2-3.3). Conclusion: Current CD4(+) cell count and failure to restore CD4(+) cell count both associated with infection and noninfection-related cancer. Viral suppression associated with lower risk of infection-related cancer. Early HIV detection and early adherent ART remain essential for cancer prevention.
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35. |
- Marklund, Emelie, et al.
(author)
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Longitudinal Follow Up of Immune Responses to SARS-CoV-2 in Health Care Workers in Sweden With Several Different Commercial IgG-Assays, Measurement of Neutralizing Antibodies and CD4+ T-Cell Responses.
- 2021
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In: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12
-
Journal article (peer-reviewed)abstract
- The risk of SARS-CoV-2 infection among health care workers (HCWs) is a concern, but studies that conclusively determine whether HCWs are over-represented remain limited. Furthermore, methods used to confirm past infection vary and the immunological response after mild COVID-19 is still not well defined.314 HCWs were recruited from a Swedish Infectious Diseases clinic caring for COVID-19 patients. IgG antibodies were measured using two commercial assays (Abbot Architect nucleocapsid (N)-assay and YHLO iFlash-1800 N and spike (S)-assays) at five time-points, from March 2020 to January 2021, covering two pandemic waves. Seroprevalence was assessed in matched blood donors at three time-points. More extensive analyses were performed in 190 HCWs in September/October 2020, including two additional IgG-assays (DiaSorin LiaisonXL S1/S2 and Abbot Architect receptor-binding domain (RBD)-assays), neutralizing antibodies (NAbs), and CD4+ T-cell reactivity using an in-house developed in vitro whole-blood assay based on flow cytometric detection of activated cells after stimulation with Spike S1-subunit or Spike, Membrane and Nucleocapsid (SMN) overlapping peptide pools.Seroprevalence was higher among HCWs compared to sex and age-matched blood donors at all time-points. Seropositivity increased from 6.4% to 16.3% among HCWs between May 2020 and January 2021, compared to 3.6% to 11.9% among blood donors. We found significant correlations and high levels of agreement between NAbs and all four commercial IgG-assays. At 200-300 days post PCR-verified infection, there was a wide variation in sensitivity between the commercial IgG-assays, ranging from <30% in the N-assay to >90% in the RBD-assay. There was only moderate agreement between NAbs and CD4+ T-cell reactivity to S1 or SMN. Pre-existing CD4+ T-cell reactivity was present in similar proportions among HCW who subsequently became infected and those that did not.HCWs in COVID-19 patient care in Sweden have been infected with SARS-CoV-2 at a higher rate compared to blood donors. We demonstrate substantial variation between different IgG-assays and propose that multiple serological targets should be used to verify past infection. Our data suggest that CD4+ T-cell reactivity is not a suitable measure of past infection and does not reliably indicate protection from infection in naive individuals.
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36. |
- Marklund, Emelie, et al.
(author)
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Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders.
- 2020
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 15:10
-
Journal article (peer-reviewed)abstract
- To accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset.SARS-CoV-2-specific IgG antibody levels were quantified using two clinically validated and widely used commercial serological assays (Architect, Abbott Laboratories and iFlash 1800, YHLO), detecting antibodies against the spike and nucleocapsid proteins.Forty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P = 0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset.Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys.
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37. |
- Naver, Lars, et al.
(author)
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Prophylaxis and treatment of HIV-1 infection in pregnancy: Swedish Recommendations 2010
- 2011
-
In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 43:6-7, s. 411-423
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Research review (peer-reviewed)abstract
- Prophylaxis and treatment with antiretroviral drugs and the use of elective caesarean section have resulted in a very low mother-to-child transmission of human immunodeficiency virus (HIV) during recent years. The availability of new antiretroviral drugs, updated general treatment guidelines and increasing knowledge of the importance of drug resistance, have necessitated regular revisions of the "Prophylaxis and treatment of HIV-1 infection in pregnancy" recommendations. For these reasons, The Swedish Reference Group for Antiviral Therapy (RAV) updated the 2007 recommendations at an expert meeting that took place on 25 March 2010. The most important revisions from the previous recommendations are: (1) it is recommended that treatment during pregnancy starts at the latest at gestational week 14-18; (2) ongoing efficient treatment at confirmed pregnancy may, with a few exceptions, be continued; (3) lopinavir/r and atazanavir/r are equally recommended protease inhibitors; (4) if maternal HIV RNA is >50 copies/ml close to delivery, a planned caesarean section, intravenous zidovudine, oral nevirapine for the mother and post-exposure prophylaxis for the infant with 3 antiretroviral drugs are recommended; (5) for delivery at <34 gestational weeks, intravenous zidovudine and oral nevirapine for the mother and at 48-72 h for the infant is recommended, in addition to other prophylaxis; (6) intravenous zidovudine is not recommended when HIV RNA is <50 copies/ml and a caesarean section is performed; (7) it is recommended that prophylaxis for the infant is started within 4 h; (8) prophylactic zidovudine for the infant may be administered twice daily instead of 4 times a day, as was the case previously; and (9) the number of sampling occasions for the infant has been decreased.
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38. |
- Navér, Lars, et al.
(author)
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Prophylaxis and treatment of HIV-1 infection in pregnancy: Swedish recommendations 2013.
- 2014
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In: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 46:6, s. 401-11
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Journal article (peer-reviewed)abstract
- Prophylaxis and treatment with antiretroviral drugs and elective caesarean section delivery have resulted in very low mother-to-child transmission of HIV during recent years. Updated general treatment guidelines and increasing knowledge about mother-to-child transmission have necessitated regular revisions of the recommendations for the prophylaxis and treatment of HIV-1 infection in pregnancy. The Swedish Reference Group for Antiviral Therapy (RAV) updated the recommendations from 2010 at an expert meeting on 11 September 2013. The most important revisions are the following: (1) ongoing efficient treatment at confirmed pregnancy may, with a few exceptions, be continued; (2) if treatment is initiated during pregnancy, the recommended first-line therapy is essentially the same as for non-pregnant women; (3) raltegravir may be added to achieve rapid reduction in HIV RNA; (4) vaginal delivery is recommended if at > 34 gestational weeks and HIV RNA is < 50 copies/ml and no obstetric contraindications exist; (5) if HIV RNA is < 50 copies/ml and delivery is at > 34 gestational weeks, intravenous zidovudine is not recommended regardless of the delivery mode; (6) if HIV RNA is > 50 copies/ml close to delivery, it is recommended that the mother should undergo a planned caesarean section, intravenous zidovudine, and oral nevirapine, and the infant should receive single-dose nevirapine at 48-72 h of age and post-exposure prophylaxis with 2 drugs; (7) if delivery is preterm at < 34 gestational weeks, a caesarean section delivery should if possible be performed, with intravenous zidovudine and oral nevirapine given to the mother, and single-dose nevirapine given to the infant at 48-72 h of age, as well as post-exposure prophylaxis with 2 additional drugs.
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39. |
- Naver, L., et al.
(author)
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Prophylaxis and treatment of HIV-1 infection in pregnancy - Swedish Recommendations 2017
- 2018
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In: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 50:7, s. 495-506
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Journal article (peer-reviewed)abstract
- Prophylaxis and treatment with antiretroviral drugs have resulted in a very low rate of mother-to-child transmission (MTCT) of HIV during recent years. Registration of new antiretroviral drugs, modification of clinical praxis, updated general treatment guidelines and increasing knowledge about MTCT have necessitated regular revisions of the recommendations for Prophylaxis and treatment of HIV-1 infection in pregnancy'. The Swedish Reference Group for Antiviral Therapy (RAV) has updated the recommendations from 2013 at an expert meeting 19 September 2017. In the new text, current treatment guidelines for non-pregnant are considered. The most important revisions are that: (1) Caesarean section and infant prophylaxis with three drugs are recommended when maternal HIV RNA >150 copies/mL (previously >50 copies/mL). The treatment target of undetectable HIV RNA remains unchanged <50 copies/mL; (2) Obstetric management and mode of delivery at premature rupture of the membranes and rupture of the membranes at full term follow the same procedures as in HIV negative women; (3) Vaginal delivery is recommended to a well-treated woman with HIV RNA <150 copies/mL regardless of gestational age, if no obstetric contraindications are present; (4) Treatment during pregnancy should begin as soon as possible and should continue after delivery; (5) Ongoing well-functioning HIV treatment at pregnancy start should usually be retained; (6) Recommended drugs and drug combinations have been updated.
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40. |
- Naver, Lars, et al.
(author)
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Prophylaxis and treatment of HIV infection in pregnancy, Swedish guidelines 2024
- 2024
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In: INFECTIOUS DISEASES. - 2374-4235 .- 2374-4243. ; 56:8, s. 657-668
-
Journal article (peer-reviewed)abstract
- In May 2024, the Swedish Reference Group on Antiviral Therapy updated the guidelines on management of HIV infection in pregnancy. The most important recommendations and revisions were: (i) ART during pregnancy should be started as early as possible and continue after delivery; (ii) Suppressive ART should normally not be modified; (iii) The treatment target of HIV RNA <20 copies/ml remains; (iv) Dolutegravir/emtricitabine/tenofovir DF is the first-line drug combination also in pregnant women and women planning pregnancy; (v) There is no evidence of an increased risk of neural tube defects associated with dolutegravir; (vi) Mode of delivery for women with effective ART and HIV RNA <200 copies/ml should follow standard obstetric procedures; (vii) Caesarean section is recommended if HIV RNA >= 200 copies/ml; (viii) Scalp electrode, foetal blood sampling and/or vacuum delivery should be used on strict indications, but does not necessitate intensified infant prophylaxis; (ix) Management and mode of delivery in case of premature or full-term rupture of membranes should follow standard obstetric procedures; (x) Recommended infant antiretroviral prophylaxis has been updated; (xi) The duration of infant antiretroviral prophylaxis (gestational age >= 35 weeks and mother on effective ART and HIV RNA <200 copies/ml) has been changed from 4 to 2 weeks; (xii) Infants born to women with HIV RNA >= 200 copies/ml should receive 4 weeks of combination prophylaxis; (xiii) Fertility evaluation and assisted reproduction should be offered to women on suppressive ART according to the same principles as for other women; (xiv) Women living with HIV should still be advised against breastfeeding; (xv) Women who nevertheless opt to breastfeed should be offered intensified support and follow-up.
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41. |
- Patel, H., et al.
(author)
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Proteomic blood profiling in mild, severe and critical COVID-19 patients
- 2021
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
-
Journal article (peer-reviewed)abstract
- The recent SARS-CoV-2 pandemic manifests itself as a mild respiratory tract infection in most individuals, leading to COVID-19 disease. However, in some infected individuals, this can progress to severe pneumonia and acute respiratory distress syndrome (ARDS), leading to multi-organ failure and death. This study explores the proteomic differences between mild, severe, and critical COVID-19 positive patients to further understand the disease progression, identify proteins associated with disease severity, and identify potential therapeutic targets. Blood protein profiling was performed on 59 COVID-19 mild (n=26), severe (n=9) or critical (n=24) cases and 28 controls using the OLINK inflammation, autoimmune, cardiovascular and neurology panels. Differential expression analysis was performed within and between disease groups to generate nine different analyses. From the 368 proteins measured per individual, more than 75% were observed to be significantly perturbed in COVID-19 cases. Six proteins (IL6, CKAP4, Gal-9, IL-1ra, LILRB4 and PD-L1) were identified to be associated with disease severity. The results have been made readily available through an interactive web-based application for instant data exploration and visualization, and can be accessed at https://phidatalab-shiny.rosalind.kcl.ac.uk/COVID19/. Our results demonstrate that dynamic changes in blood proteins associated with disease severity can potentially be used as early biomarkers to monitor disease severity in COVID-19 and serve as potential therapeutic targets.
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42. |
- Robertson, Josefina, et al.
(author)
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Increased immune activation and signs of neuronal injury in HIV-negative people on preexposure prophylaxis.
- 2021
-
In: AIDS (London, England). - 1473-5571 .- 0269-9370. ; 35:13, s. 2129-2136
-
Journal article (peer-reviewed)abstract
- Persistent immune activation in the central nervous system and systemically are common in people living with HIV (PLHIV) despite antiretroviral therapy. It is not known whether this is generated by HIV replication or by other components such as coinfections and lifestyle-related factors.The aim of this study was to determine the importance of different factors; it is crucial to find well matched HIV-negative controls. In this context, HIV-negative persons on preexposure prophylaxis (PrEP) may constitute a suitable control group to PLHIV with similar lifestyle-related factors.Cerebrospinal fluid (CSF) and blood were collected from 40 HIV-negative persons on PrEP and 20 controls without PrEP. Biomarkers of immune activation, blood--brain barrier (BBB) integrity and neuronal injury were analysed.CSF and serum β2-microglobulin, serum neopterin and CSF neurofilament light protein were higher in persons on PrEP compared with controls. Furthermore, persons on PrEP had higher CSF/plasma albumin ratio, and matrix metalloproteinase-3 concentrations, indicating BBB dysfunction. Of persons on PrEP, 90% were cytomegalovirus (CMV)-positive compared to 65% of the controls. CMV-positive individuals as a group had higher levels of serum β2-microglobulin than CMV-negative individuals (P<0.05). Drug users had higher serum β2-microglobulin compared to nonusers (P<0.01).HIV-negative persons on PrEP had higher levels of biomarkers for immune activation, BBB impairment and neuronal injury, compared with volunteers without PrEP. Moreover, serum β2-microglobulin was higher in CMV-positive than in CMV-negative individuals and in drug users compared with nonusers. These findings are important to consider when analysing immune activation and CNS injury in PLHIV, and emphasize the importance of appropriate controls.
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43. |
- Soderholm, J., et al.
(author)
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Lower risk of multiple sclerosis in patients with chronic hepatitis C: a nationwide population-based registry study
- 2019
-
In: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 266:9, s. 2208-2215
-
Journal article (peer-reviewed)abstract
- Background Multiple sclerosis (MS) is an immune-mediated neurological disease that causes demyelination. The etiology is unknown, but patients with a previous viral infection, such as Epstein-Barr virus, have been shown to be at a higher risk of developing MS. In contrast, people living with HIV have a lower risk of developing MS. Hepatitis C virus (HCV) mainly infects the liver, but patients with HCV can experience several extrahepatic manifestations and studies have shown an association with several autoimmune conditions such as neuropathy and myelitis. The present study aimed to investigate the risk of MS in patients with chronic HCV infection compared with matched comparators. Methods Patients were identified using the nationwide Swedish inpatient (2001-2013) and outpatient care registers (2001-2013) for HCV (B18.2) and MS (G35) according to the International Classification of Diseases-10. Up to five comparators (matched on age/sex/place of residency) were drawn from the general population for each HCV patient. Follow-up started at the first HCV visit from 2001 and the patients' accrued person-time until death, emigration or 31 December 2013. Risk of MS diagnosis was calculated as standardized incidence ratio (SIR) with 95% confidence intervals (CIs). Results HCV patients were at lower risk of MS diagnosis (SIR 0.37; 95% CI 0.26-0.50). The incidence of MS during the study in the HCV cohort was 0.087% compared with 0.27% in the matched comparator cohort. Conclusion Surprisingly, these data suggest HCV patients to have a lower risk of MS diagnosis.
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44. |
- Sourander, Birger, et al.
(author)
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No effect of remdesivir or betamethasone on upper respiratory tract SARS-CoV-2 RNA kinetics in hospitalised COVID-19 patients: a retrospective observational study
- 2022
-
In: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 54:10, s. 703-712
-
Journal article (peer-reviewed)abstract
- Background The viral kinetics of SARS-CoV-2 has been considered clinically important. While remdesivir and corticosteroids are recommended for COVID-19 patients requiring oxygen support, there is a limited number of published reports on viral kinetics in hospitalised patients with COVID-19 treated with remdesivir or corticosteroids. Methods We conducted a retrospective study by collecting longitudinal samples from the nasopharynx/throat of 123 hospitalised patients (median age 55 years, 74% male) with COVID-19, to evaluate the effects of remdesivir and corticosteroid treatment on viral RNA levels. The subjects were divided into four groups: those receiving remdesivir (n = 25), betamethasone (n = 41), both (n = 15), or neither (n = 42). Time to viral RNA clearance was analysed using Kaplan-Meier plots, categorical data were analysed using Fisher's exact test, and Kruskal-Wallis for continuous data. Viral RNA decline rate was analysed using a mixed effect model. Results We found no significant difference in SARS-CoV-2 RNA decline rate or time to SARS-CoV-2 RNA clearance between the groups. Moreover, clinical status at baseline was not correlated with time to viral clearance. Conclusions Since SARS-CoV-2 RNA kinetics was not affected by treatment, repeated sampling from the upper respiratory tract cannot be used to evaluate treatment response.
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45. |
- Sörstedt, Erik, et al.
(author)
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Effect of dolutegravir in combination with Nucleoside Reverse Transcriptase Inhibitors (NRTIs) on people living with HIV who have pre-existing NRTI mutations
- 2018
-
In: International Journal of Antimicrobial Agents. - : Elsevier BV. - 0924-8579 .- 1872-7913. ; 51:5, s. 733-738
-
Journal article (peer-reviewed)abstract
- Until the introduction of dolutegravir (DTG), people living with HIV (PLWH) who have developed nucleoside reverse transcriptase inhibitor (NRTI) mutations have had few other treatment options outside of regimens based on ritonavir-boosted protease inhibitors (PI/r). Here we report treatment results among PLWH in Sweden with pre-existing NRTI mutations on antiretroviral treatment (ART) with DTG and one to two NRTIs. All PLWH on ART with DTG and one to two NRTIs with pre-existing NRTI mutations were retrospectively identified from the National InfCare HIV database. As controls, PLWH on PI/r and one to two NRTIs, matched according to Genotypic Susceptibility Score and observation time, were included. Data were collected as long as the study population was on treatment with DTG; controls were monitored for the same interval. Outcome was classified as either treatment success or failure. In total, 244 participants (122 individuals treated with DTG and 122 individuals treated with PI/r) were included. Median observation time was 78 weeks (interquartile range 50-98 weeks) for participants on DTG and 75 weeks (50-101 weeks) for individuals on PI/r. Viral failure was detected in four individuals treated with DTG and three individuals treated with PI/r, resulting in similar success rates of 96.7% and 97.5%, respectively. No new mutations were found among participants with treatment failure. DTG in combination with one to two NRTIs was as efficient as PI/r in individuals with pre-existing NRTI mutations in this setting. It may be considered an alternative to PI/r-based ART even in the presence of NRTI resistance. (c) 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
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46. |
- Sörstedt, Erik, et al.
(author)
-
Impact of pre-antiretroviral treatment HIV-RNA on time to successful virological suppression and subsequent virological failure - two nationwide, population-based cohort studies.
- 2023
-
In: AIDS (London, England). - : LIPPINCOTT WILLIAMS & WILKINS. - 1473-5571 .- 0269-9370. ; 37:2, s. 279-286
-
Journal article (peer-reviewed)abstract
- The impact of pre-antiretroviral treatment (ART) HIV-RNA on time to successful virological suppression and subsequent failure in HIV patients remains poorly investigated.We used the Swedish InfCareHIV database and the Danish HIV Cohort Study to evaluate impact of pre-ART HIV-RNA on primary virological suppression (HIV-RNA < 50copies/ml) and risk of secondary virological failure (two consecutive HIV-RNA > 200copies/ml or one >1000copies/ml). The study included 3366 Swedish and 2050 Danish ART naïve individuals who initiated ART in the period 2000-2018. We used Kaplan-Meier estimates and Cox regression analyses to estimate absolute risks and hazard ratios.In both cohorts, more than 95% of patients with a pre-ART HIV-RNA <100 000copies/ml obtained virological suppression within the first year after ART initiation contrasting 74% (Sweden) and 86% (Denmark) in those with HIV-RNA >1 000 000copies/ml. Almost all patients obtained virological suppression after four years irrespective of pre-ART HIV-RNA. In contrast, we observed no substantial impact of pre-ART HIV-RNA on risk of virological failure once virological suppression was obtained.High pre-ART HIV-RNA is strongly associated with increased time to successful virological suppression, but pre-ART HIV-RNA has no impact on risk of subsequent virological failure.
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47. |
- Sörstedt, Erik, et al.
(author)
-
Viral blips during suppressive antiretroviral treatment are associated with high baseline HIV-1 RNA levels
- 2016
-
In: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 16
-
Journal article (peer-reviewed)abstract
- Background: Many HIV-1-infected patients on suppressive antiretroviral therapy (ART) have transiently elevated HIV RNA levels. The clinical significance of these viral blips is uncertain. We have determined the incidence of blips and investigated important associations in the Swedish HIV-cohort. Methods: HIV-1-infected ART naive adults who commenced ART 2007-2013 were retrospectively included. Viral blips were defined as a transient viral load between 50 and 500 copies/mL Subjects not suppressed after six months on ART were excluded. Results: Viral blips were found in 76/735 included subjects (10.3 %) and in 90/4449 samples (2.0 %). Median blip viral load was 76 copies/mL (range 56-138). Median follow-up time was 170 weeks (range 97-240). Baseline viral load was higher in subjects with viral blips (median log(10) 4.85 copies/mL) compared with subjects without blips (median log(10) 4.55 copies/mL) (p < 0.01). There was a significant association between viral blips and risk for subsequent virological failure (p < 0.001). Conclusions: The Swedish national HIV-cohort has a low incidence of viral blips (10 %). Blips were associated with high baseline viral load and an increased risk of subsequent virological failure.
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48. |
- Tyrberg, Erika, et al.
(author)
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The effect of vitamin B supplementation on neuronal injury in people living with HIV: a randomized controlled trial
- 2022
-
In: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 4:6
-
Journal article (peer-reviewed)abstract
- Effective antiretroviral therapy has radically changed the course of the HIV pandemic. However, despite efficient therapy, milder forms of neurocognitive symptoms are still present in people living with HIV. Plasma homocysteine is a marker of vitamin B deficiency and has been associated with cognitive impairment. People living with HIV have higher homocysteine concentrations than HIV-negative controls, and we have previously found an association between plasma homocysteine concentration and CSF concentration of neurofilament light protein, a sensitive marker for ongoing neuronal injury in HIV. This prompted us to perform this randomized controlled trial, to evaluate the effect of vitamin B supplementation on neuronal injury in a cohort of people living with HIV on stable antiretroviral therapy. At the Department of Infectious Diseases at Sahlgrenska University Hospital in Gothenburg, Sweden, 124 virally suppressed people living with HIV were screened to determine eligibility for this study. Sixty-one fulfilled the inclusion criteria by having plasma homocysteine levels at or above 12 mu mol/l. They were randomized (1:1) to either active treatment (with cyanocobalamin 0.5 mg, folic acid 0.8 mg and pyridoxine 3.0 mg) q.d. or to a control arm with a cross over to active treatment after 12 months. Cognitive function was measured repeatedly during the trial, which ran for 24 months. We found a significant correlation between plasma neurofilament light protein and plasma homocysteine at screening (n = 124, r = 0.35, P < 0.0001). Plasma homocysteine levels decreased by 35% from a geometric mean of 15.7 mu mol/l (95% confidence interval 14.7-16.7) to 10.3 mu mol/l (95% confidence interval 9.3-11.3) in the active treatment arm between baseline and Month 12. No significant change was detected in the control arm during the same time period [geometric mean 15.2 (95% confidence interval 14.3-16.2) versus geometric mean 16.5 mu mol/l (95% confidence interval 14.7-18.6)]. A significant difference in change in plasma homocysteine levels was seen between arms at 12 months [-40% (95% confidence interval -48 to -30%), P < 0.001]. However, no difference between arms was seen in either plasma neurofilament light protein levels [-6.5% (-20 to 9%), P = 0.39], or cognitive measures [-0.08 (-0.33 to 0.17), P = 0.53]. Our results do not support a vitamin B-dependent cause of the correlation between neurofilament light protein and homocysteine. Additional studies are needed to further elucidate this matter. Tyrberg et al. report the results of a randomized controlled trial investigating the effect of vitamin B supplementation on neuronal injury in people living with HIV with effective antiretroviral therapy. Supplementation decreased levels of homocysteine but not neuronal injury measured by neurofilament light protein.
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49. |
- Ulfhammer, Gustaf, et al.
(author)
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Persistent central nervous system immune activation following more than 10 years of effective HIV antiretroviral treatment
- 2018
-
In: AIDS. - 1473-5571 .- 0269-9370. ; 32:15, s. 2171-2178
-
Journal article (peer-reviewed)abstract
- Objective: Low-grade immune activation is common in people living with HIV (PLHIV), despite long-term viral suppression by antiretroviral therapy (ART). The clinical significance of this activation remains unclear. The aim of this study was to examine residual intrathecal immune activation in relation to signs of neuronal injury and neurocognitive impairment in PLHIV who had been virally suppressed on ART for more than 10 years. Design/methods: Twenty neuroasymptomatic PLHIV on suppressive ART for a median of 13.2 years were retrospectively identified from the longitudinal prospective Gothenburg HIV cerebrospinal fluid (CSF) study. HIV-RNA, neopterin, and neurofilament light protein (NFL) levels were measured in paired plasma and CSF samples. Pretreatment samples were available for 14 patients. Cognitive function was assessed by CogState at follow-up. Results: CSF neopterin decreased from a median (IQR) of 17.8 (10.6 - 29.7) to 6.1 (4.6 - 8.0) nmol/l during treatment (P < 0.001). In 11 out of 20 participants (55%), CSF neopterin levels were above the upper normal reference limit (5.8 nmol/l) at followup. Age-adjusted CSF NFL decreased to within-normal levels from a median of (IQR) 1179 (557 - 2707) to 415 (292 - 610) ng/l (P < 0.001). No significant correlations were found between CSF neopterin and CSF NFL or neurocognitive performance. Conclusion: Although CSF neopterin decreased significantly, more than 50% of the patients had CSF concentrations above the upper normal reference value despite more than 10 years of suppressive ART. We found no correlation between CSF neopterin, CSF NFL or neurocognitive performance at follow-up, indicating that low-grade immune activation during suppressive ART may be clinically benign.
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50. |
- Ulfhammer, Gustaf, et al.
(author)
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Persistent CNS immune activation following > 10 years of effective HIV antiretroviral treatment.
- 2018
-
In: AIDS (London, England). - 1473-5571. ; 32:15, s. 2171-2178
-
Journal article (peer-reviewed)abstract
- Low-grade immune activation is common in people living with HIV (PLHIV), despite long-term viral suppression by antiretroviral therapy (ART). The clinical significance of this activation remains unclear. The aim of this study was to examine residual intrathecal immune activation in relation to signs of neuronal injury and neurocognitive impairment in PLHIV who had been virally suppressed on ART > 10 years.Twenty neuroasymptomatic PLHIV on suppressive ART for a median of 13.2 years were retrospectively identified from the longitudinal prospective Gothenburg HIV cerebrospinal fluid (CSF) study. HIV-RNA, neopterin, and neurofilament light protein (NFL) levels were measured in paired plasma and CSF samples. Pre-treatment samples were available for 14 subjects. Cognitive function was assessed by CogState at follow-up.CSF neopterin decreased from a median (IQR) of 17.8 (10.6-29.7) to 6.1 (4.6-8.0) nmol/L during treatment (p<0.001). In 11 out of 20 participants (55%), CSF neopterin levels were above the upper normal reference limit (5.8nmol/L) at follow-up. Age-adjusted CSF NFL decreased to within normal levels from a median of (IQR) 1179 (557-2707) to 415 (292-610) ng/L (p<0.001). No significant correlations were found between CSF neopterin and CSF NFL or neurocognitive performance.Although CSF neopterin decreased significantly, >50% of the subjects had CSF concentrations above the upper normal reference value despite >10 years of suppressive ART. We found no correlation between CSF neopterin, CSF NFL or neurocognitive performance at follow up, indicating that low grade immune activation during suppressive ART may be clinically benign.
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