Dag Henrik Reikvam

• MacLeod, Julia; Gudissa, Fikadu G.; Jeylan, Asiya; Berhe, Nega; Mekonnen, Hailemichael Desalegn & Rossvoll, Lasse Olsen [Show all 10 contributors for this article] (2026). A Distinct Immune Signature Characterizes Cirrhosis in Ethiopian Individuals With Chronic <scp>HBV</scp> Infection. Alimentary Pharmacology and Therapeutics. ISSN 0269-2813. doi: 10.1111/apt.70816. Full text in Research Archive Show summary

  ABSTRACT Background and Aims The immune cell phenotype of African patients living with chronic hepatitis B virus (HBV) infection is rarely described, despite high infection rates. This study investigated the differences in immune cell phenotypes in four distinct clinical phases of disease in an Ethiopian cohort. Methods Two hundred eighty‐seven patients with untreated HBV infection, and no human immunodeficiency virus and hepatitis C virus infection, were included at Adama Hospital, Ethiopia. Patients were categorized based on clinical parameters into the following groups: low‐replicative infection, “greyzone”, active hepatitis, and cirrhosis. Whole blood samples were cryopreserved using Cytodelics Whole Blood Cell Stabilizer and analysed using two high‐dimensional flow cytometry panels to define immune cell phenotypes. Results Patients with cirrhosis displayed a distinct immunophenotype compared to other phases of chronic HBV infection with an increase in monocytes and a reduction in all lymphocytes alongside a shift from a mature to a naïve phenotype in NK cells, CD4 + T cells, and B cells. The emergence of activated CD38 + HLA‐DR + cells across lymphocyte lineages defined patients with cirrhosis and the frequency of these double positive cells correlated positively with the AST to Platelet Ratio Index used as a measure of cirrhosis severity. Conclusions HBV‐associated cirrhosis in Ethiopia displayed a unique immunophenotype, in which the frequency of CD38 + HLA‐DR + NK cells and T cells correlated strongly with the severity of cirrhosis.

• Myhre, Anders Eivind; Meyer-Myklestad, Malin Holm; Gullaksen, Hanne Hestdal; Søgaard, Ole S.; Tolstrup, Martin & Salgado, Maria [Show all 51 contributors for this article] (2026). Long-term HIV-1 remission achieved through allogeneic haematopoietic stem cell transplant from a CCR5Δ32/Δ32 sibling donor. Nature Microbiology. 11, p. 1374–1386. doi: 10.1038/s41564-026-02304-8. Full text in Research Archive Show summary

  Only few cases of human immunodeficiency virus (HIV) remission have been reported after allogeneic haematopoietic stem cell transplantation (HSCT), mostly involving stem cell donors with the homozygous CCR5Δ32 (CCR5Δ32/Δ32) mutation, which confers resistance to CCR5-tropic HIV-1. Here we report the case of a 63-year-old man in off-treatment HIV remission, 5 years after HSCT with a CCR5Δ32/Δ32 sibling donor for myelodysplastic syndrome. In-depth clinical characterization including virological and immunological analyses of peripheral blood, gut and bone marrow samples revealed that full donor chimerism was achieved. Antiretroviral therapy was discontinued after 24 months, and 48 months after HSCT, no intact HIV DNA was detected in blood or gut biopsies. Replication-competent virus and HIV-specific T cell responses were absent, and HIV antibody responses showed a gradual decline. Full donor chimerism in the gut, which is the primary viral reservoir, underscores the likelihood of a cure.

• Holmberg, Marte; Niehrs, Annika; Dalgard, Olav; Berhe, Nega; Desalegn, Hailemichael & Aleman, Soo [Show all 20 contributors for this article] (2026). Hepatic flares, their immune signatures, and ALT variability after nucleos(t)ide analogue cessation in HBeAg-negative hepatitis B. JHEP Reports. doi: 10.1016/j.jhepr.2026.101875. Full text in Research Archive Show summary

  Background and aims: Hepatic flares frequently occur after nucleos(t)ide analogue (NA) cessation in patients with chronic hepatitis B (CHB) and can be beneficial ("good flares") or harmful ("bad flares"). We characterised flares after NA cessation aiming to identify predictors and immunological correlates of good and bad flares. Methods: This study was nested in the prospective Nuc-Stop study, in which 127 patients with e-antigen negative CHB discontinued NA treatment with a 36-month follow-up. Flares were defined as an ALT increase >2× the upper limit of normal or >2× baseline. Predictors of flares were identified by logistic regression. In 32 patients with flares without treatment restart, we compared clinical characteristics and soluble immune marker profiles of good flares (hepatitis B surface antigen (HBsAg) loss or >1 log10 decline or sustained virological control) and bad flares (neither HBsAg decline nor virological control). Results: Flares occurred in 58.3% of patients. Age (per 1-year increment; adjusted odds ratio (aOR), 1.07; 95% confidence interval (CI) 1.02-1.12) and end-of-treatment HBsAg level (per 1 log10 IU/mL increment; aOR, 2.09; 95% CI 1.20-3.62) independently predicted flares. Good flares displayed less ALT variability after the initial spike than bad flares (standard deviation 9.7 vs. 22.7 U/L, p=0.002). Analysis of soluble immune markers confirmed distinct clusters for good and bad flares at end-of-treatment, with higher serum levels of specific proteins in good flares (e.g. IL-13, TRAIL) and bad flares (e.g. CXCL11, OPG, TNF). Conclusions: Flares occurred in over half the patients after NA cessation and were associated with age and end-of-treatment HBsAg levels. ALT variability following the initial flare and soluble marker profiles might serve as prognostic factors and distinguish good from bad flares. Impact and implications: Nucleos(t)ide analogue cessation in HBeAg-negative chronic hepatitis B may facilitate functional cure, but hepatic flares are common and potentially detrimental, making careful patient selection essential. In this prospective, multicentre trial, flares occurred in over half of the patients, with severe flares in 12.6%. Increasing age and higher end-of-treatment HBsAg levels were predictors of flares and should be considered when deciding on treatment discontinuation. Close monitoring, particularly during the first six months, is critical for safe patient management, while ALT variability following the initial flare and soluble immune markers may help differentiate good from bad flares and guide retreatment decisions.

• Kildal, Anders Benjamin; Ueland, Thor; Mirlashari, Mohammad Reza; Nissen-Meyer, Lise Sofie; Granerud, Beathe Kiland & Riise, Anne Margarita Dyrhol [Show all 44 contributors for this article] (2026). Serial blood serum measurements of calprotectin and deoxyribonuclease in COVID-19 patients during hospitalization and recovery until one year: a prospective, multicenter, observational study. BMC Infectious Diseases. 26. doi: 10.1186/s12879-026-12939-x. Full text in Research Archive Show summary

  Objectives: To examine circulating calprotectin and deoxyribonuclease (DNase) serum levels during hospitalization in COVID-19 patients, their continuity post-discharge and dynamics in relation to disease severity. Methods: Serum levels were measured in samples collected from 252 COVID-19 patients during hospitalization (admission, days 3–5 and 7–10), at 3 months and after 1 year, and related to admission to intensive care unit (ICU) or high dependency unit (HDU), and 60-day total mortality. Results: During hospitalization, calprotectin and DNase levels were significantly elevated compared to healthy controls (HC). Calprotectin was increased in ICU/HDU patients compared to those at wards during hospitalization and in non-survivors compared to survivors during prolonged hospitalization. High calprotectin levels at admission were associated with male sex, PaO2/FiO2 ratio and national COVID-19 wave 2 and 3 compared to wave 1. High admission levels of both calprotectin and ferritin were associated with an approximately twofold higher odds ratio for ICU/HDU admission than either marker alone. DNase was lower at admission in non-survivors compared to survivors. Post-discharge, DNase but not calprotectin levels remained elevated extending to 1-year follow-up compared to HC. Conclusions: COVID‑19 non‑survivors showed persistently higher calprotectin levels during prolonged hospitalization, and elevated admission calprotectin was associated with later pandemic waves and poorer oxygenation. Incorporating calprotectin with ferritin improved prediction of ICU/HDU admission. DNase levels were lower at admission in non‑survivors, while overall DNase remained elevated from hospitalization through 1‑year follow‑up compared with HC, suggesting a possible role in long‑term COVID‑19–related immune alterations.

• Dongelmans, Edo; Hirode, Grishma; Bӧmmel, Florian van; Jeng, Wen-Juei; Chien, Rong-Nan & Chen, Chien-Hung [Show all 34 contributors for this article] (2026). Long-term outcomes after nucleos(t)ide analogue cessation in chronic hepatitis B – follow-up from the RETRACT-B cohort. Journal of Hepatology. ISSN 0168-8278. doi: 10.1016/j.jhep.2026.03.030. Full text in Research Archive
• Bajer, Lukas; Polakovicova, Petra; Heczkova, Marie; Holm, Kristian; Hole, Mikal Jacob & Hlavaty, Mojmir [Show all 19 contributors for this article] (2025). Geography-independent mucosal microbiota alterations in primary sclerosing cholangitis persist after liver transplantation. JHEP Reports. 8(4). doi: 10.1016/j.jhepr.2025.101716. Full text in Research Archive Show summary

  Background & Aims Primary sclerosing cholangitis (PSC)-associated alterations of fecal gut microbiota have already been described, but data on the mucosal microbiota are still limited. We aimed to further define disease-specific mucosal microbial patterns independent of geography and assess the relationship to liver transplantation (LTx), gut inflammation (inflammatory bowel disease), and PSC recurrence (rPSC). Methods We performed 16S ribosomal RNA gene (V3–V4) sequencing of ileocolonic biopsies from 115 patients with PSC (pre-LTx), 159 liver-transplanted patients (post_LTx, recurrence occurred in 38), and 96 healthy controls (HC) from Norway and the Czech Republic. Results Alpha diversity was lower in all PSC groups compared with HC. Elastic net models discriminated pre_LTx (AUC ileum 0.97; colon 0.93; p <0.001) and post_LTx PSC patients (AUC ileum 0.97; colon 0.97; p <0.001) from HC, and distinguished pre_LTx from post_LTx (AUC ileum 0.83; colon 0.83; p <0.001). The shared, cohort-independent PSC microbiota was dominated by Enterococcus, Pseudomonas, Veillonella, Klebsiella, and Streptococcus, while several common commensals were underrepresented. A microbial dysbiosis index calculated from PSC-associated genera correlated negatively with alpha diversity and serum albumin, while a positive correlation was observed with markers of cholestatic disease (ALP, GGT) and liver fibrosis (APRI). There were no associations with the presence of inflammatory bowel disease or fecal calprotectin. Differences between post-LTx patients with and without recurrence were limited, but several genera deregulated in pre-LTx PSC (Klebsiella, Bilophila, Coprococcus, Odoribacter) showed similar trends in rPSC. Conclusions Our findings in two European countries revealed a distinct mucosal microbiota composition associated with PSC that persists after LTx. These microbial patterns correlate with the severity of liver injury in PSC but not with markers of intestinal inflammation. Impact and implications This study provides an extensive evaluation of mucosa-associated microbiota in primary sclerosing cholangitis (PSC) before and after liver transplantation across two European cohorts. The persistence of PSC-related dysbiosis after transplantation highlights the importance of the gut–liver axis in PSC and supports further investigation into microbiota-driven mechanisms. Together with the strong association between microbiota composition and markers of cholestasis and fibrosis, this suggests potential clinical utility as an indicator of disease activity or even as a target for prevention or therapy.

• Kaarbø, Mari; Yang, Mingyi; Meyer-Myklestad, Malin Holm; Sundaram, Arvind; Sousa, Mirta & Sharma, Animesh [Show all 13 contributors for this article] (2025). Transcriptomic and proteomic profiling reveal immune and metabolic dysregulation in the colonic mucosa of people living with HIV with incomplete immune recovery. Frontiers in Immunology. 16. doi: 10.3389/fimmu.2025.1635523. Full text in Research Archive Show summary

  Background People living with HIV are called immunological non-responders (INR) when their CD4+ T cell count is not restored to immunocompetent levels, despite successful viral suppression. INR have increased risk of progression to AIDS, non-AIDS related morbidity, and death. Impaired mucosal barrier function is a prevailing hypothesis for why INR among people with HIV (PWH) have persistently low CD4+ T cell counts. Objective To understand the molecular mechanisms behind incomplete immune recovery in INR, we analyzed gene regulation and protein expression in gut tissues from INR, immunological responders (IR) and healthy controls (HC). Methods The transcriptome was assessed by RNA-sequencing (RNA-seq) and the proteome was examined using shotgun proteomic mass spectrometry in mucosal biopsies from the sigmoid colon and terminal ileum. Results In INR compared to IR, we identified 3326 differentially expressed genes (DEGs) in the colon while no DEGs were observed in the ileum. Gene ontology (GO) analyses revealed that the DEGs in colon of INR, compared to IR, predominantly involved pathways related to immune response, metabolism, and cellular processes. Notably, GO analysis highlighted downregulation of genes associated with B cell-mediated immunity and adaptive responses in INR. Deconvolution analysis indicated that these transcriptomic changes were not solely due to shifts in immune cell composition. Proteomic analysis supported these findings, showing more differential protein composition between INR and IR in colon than ileum. These proteins are associated with the regulation of adaptive immune signaling and essential cellular processes, including cell signaling, tissue repair, and growth, all of which are characteristic features of inflammatory bowel disease (IBD). Conclusion Our findings suggest that incomplete immune recovery during anti-retroviral therapy in PWH is associated with specific dysregulations in the molecular environment of the sigmoid colon, which may share mechanisms with IBD. The identified macromolecules may serve as potential targets for adjuvant treatment to improve the prognosis for INR.

• Ghorbani, Mahin; Kvedaraite, Agne; Al-Manei, Khaled; Too, Choon Boon; Cederberg, Susanne & Johannessen, Asgeir [Show all 12 contributors for this article] (2025). Oral Microbiome Diversity Matters on Nucleos(t)ide Analogue Cessation in Chronic Hepatitis B. Journal of Infectious Diseases. ISSN 0022-1899. doi: 10.1093/infdis/jiaf591. Full text in Research Archive Show summary

  Abstract Background Withdrawal of nucleos(t)ide analogue (NUC) therapy in hepatitis B e antigen (HbeAg)-negative chronic hepatitis B (CHB) may lead to functional cure in a subset of patients. Although gut microbiota is known to influence both CHB progression and treatment outcomes, the oral microbiome in NUC cessation remains unexplored. Methods This longitudinal study explored the oral microbiome in patients with CHB on NUC therapy &gt; 2 years having a planned NUC cessation. Oral microbiome composition was analyzed in 110 saliva samples across 7 time points from 18 HBeAg-negative patients with 36 months follow-up. Favorable outcome was defined as either HBsAg loss or decline of &gt; 1 log10 or sustained off-therapy HBV DNA level &lt; 2000 IU/mL during year 3. Hepatic flare was defined as alanine transaminase (ALT) &gt; 80 U/L or 2 × baseline level. Results The overall microbial composition remained stable during the study period. Patients with favorable outcome showed consistently higher alpha diversities (P &lt; .001) from baseline, with lower intersample variations across all time points (P &lt; .05), compared to unfavorable. Hepatitis B surface antigen (HBsAg), ALT, and aspartate transaminase (AST) correlated inversely with several Prevotella taxa and specific pathways (Spearman ρ &gt; −0.5, P &lt; .01). Unfavorable outcome and high HBsAg level correlated with opportunistic taxa Haemophilus parainfluenzae and Porphyromonas catoniae. Random forest model incorporating validated microbial markers predicting favorable versus unfavorable outcome achieved higher predictive performance than clinical markers alone (area under curve, 0.79 vs 0.66). Conclusions Our exploratory study suggests that oral microbiome profiling at NUC cessation in HBeAg-negative CHB could support prognostication of virological outcome. Clinical Trials Registration. NCT03681132.

• Granerud, Beathe Kiland; Kaarbø, Mari; Al-Baldawi, Huda; Heggelund, Lars; Tveita, Anders & Müller, Karl Erik [Show all 42 contributors for this article] (2025). Droplet Digital PCR or Real-Time PCR as a Method for Quantifying SARS-CoV-2 RNA in Plasma-Is There a Difference? Viruses. 17(6). doi: 10.3390/v17060772. Full text in Research Archive Show summary

  The aim of this study is to ascertain whether qRT-PCR (reverse transcriptase real-time PCR) or RT-ddPCR (reverse transcriptase digital droplet PCR) is more effective for detecting SARS-CoV-2 RNA (severe acute respiratory syndrome coronavirus 2 RNA) in blood plasma from COVID-19 (coronavirus infectious disease-19) patients. The E-gene of SARS-CoV-2 RNA was quantified using both methods in 128 plasma samples from 70 hospitalized patients, followed by a statistical analysis to compare the sensitivity and concordance between the methods. Out of the 128 samples, 89 yielded consistent results irrespective of the method used, whereas 39 samples showed discrepancies between the two different methods. RT-ddPCR frequently registered higher viral quantities compared to qRT-PCR; however, the results did not demonstrate a clear superiority in sensitivity for RT-ddPCR. Although RT-ddPCR registered higher viral quantities, this study concludes that both methods provide comparable results for detecting SARS-CoV-2 E-gene RNA in plasma.

• Kraef, Christian; Singh, Sabine; Fursa, Olga; Abutidze, Akaki; Rukhadze, Nino & Mulabdic, Velida [Show all 22 contributors for this article] (2024). Differences in integrated assessment and management of non-communicable diseases (NCDs) for people with HIV across the WHO European region. HIV Medicine. ISSN 1464-2662. doi: 10.1111/hiv.13619. Full text in Research Archive
• Viermyr, Hans-Kittil; Halvorsen, Bente; Sagen, Ellen Lund; Michelsen, Annika Elisabet; Barratt-Due, Andreas & Kåsine, Trine [Show all 73 contributors for this article] (2024). High viral loads combined with inflammatory markers predict disease severity in hospitalized COVID-19 patients: Results from the NOR-Solidarity trial. Journal of Internal Medicine. ISSN 0954-6820. 296(3), p. 249–259. doi: 10.1111/joim.13820. Full text in Research Archive Show summary

  Objectives To investigate temporal changes in the association between SARS-CoV2 viral load (VL) and markers of inflammation during hospitalization, as well as the ability of these markers alone or in combination to predict severe outcomes. Methods Serial oropharyngeal and blood samples were obtained from hospitalized COVID-19 patients (n = 160). Levels of inflammatory markers and oropharyngeal VL were measured during hospitalization (admission, days 3–5, and days 7–10) and related to severe outcomes (respiratory failure/intensive care unit admission). Results Elevated admission levels of IL (interleukin)-6, IL-33, IL-8, monocyte chemoattractant protein-1 (MCP-1), interferon-γ-induced protein 10 (IP-10), IL-1β, and IL-1Ra were associated with severe outcomes during hospitalization. Although no inflammatory markers correlated with VL at baseline, there was a significant correlation between VL and levels of IP-10 and MCP-1 at days 3–5, accompanied by IL-8 and IL-6 at days 7–10. Finally, there was a seemingly additive effect of IP-10, MCP-1, and IL-6 in predicting severe outcomes when combined with high VL at baseline. Conclusions An increasing number of inflammatory markers were associated with VL during the first 10 days of hospitalization, and several of these markers were associated with severe outcomes, in particular when combined with elevated VL. Future studies should assess the potential for combining antiviral and immunomodulatory treatment, preferably guided by viral and inflammatory biomarkers, for the selection of high-risk patients.

• Alirezaylavasani, Amin; Skeie, Linda Gail; Egner, Ingrid Marie; Chopra, Adity; Dahl, Tuva Børresdatter & Prebensen, Christian Haugland [Show all 16 contributors for this article] (2024). Vaccine responses and hybrid immunity in people living with HIV after SARS-CoV-2 breakthrough infections. npj Vaccines. 9(1), p. 1–15. doi: 10.1038/s41541-024-00972-3. Full text in Research Archive Show summary

  The COVID-19 pandemic posed a challenge for people living with HIV (PLWH), particularly immune non-responders (INR) with compromised CD4 T-cell reconstitution following antiretroviral therapy (CD4 count <350 cells per mm3). Their diminished vaccine responses raised concerns about their vulnerability to SARS-CoV-2 breakthrough infections (BTI). Our in-depth study here revealed chronic inflammation in PLWH and a limited anti-Spike IgG response after vaccination in INR. Nevertheless, the imprinting of Spike-specific B cells by vaccination significantly enhanced the humoral responses after BTI. Notably, the magnitude of cellular CD4 response in all PLWH was comparable to that in healthy donors (HD). However, the polyfunctionality and phenotype of Spike-specific CD8 T cells in INR differed from controls. The findings highlight the need for additional boosters with variant vaccines, and for monitoring ART adherence and the durability of both humoral and cellular anti-SARS-CoV-2 immunity in INR.

• Johannessen, Asgeir; Reikvam, Dag Henrik; Aleman, Soo; Berhe, Nega; Weis, Nina & Mekonnen, Hailemichael Desalegn [Show all 24 contributors for this article] (2024). Clinical trial: An open-label, randomised trial of different re-start strategies after treatment withdrawal in HBeAg negative chronic hepatitis B. Alimentary Pharmacology and Therapeutics. ISSN 0269-2813. 60(4), p. 434–445. doi: 10.1111/apt.18147. Full text in Research Archive Show summary

  Background: Stopping nucleos(t)ide analogue (NA) therapy in patients with chronic hepatitis B (CHB) may trigger a beneficial immune response leading to HBsAg loss, but clinical trials on re-start strategies are lacking. Aim: To assess whether it is beneficial to undergo a prolonged flare after NA cessation. Methods: One-hundred-and-twenty-seven patients with HBeAg negative, non-cirrhotic CHB with at least 24 months of viral suppression on NA therapy were included. All study participants stopped antiviral therapy and were randomised to either low-threshold (ALT > 80 U/L and HBV DNA > 2000 IU/mL) or high-threshold (ALT > 100 U/L for >4 months, or ALT > 400 U/L for >2 months) for the re-start of therapy. The primary endpoint was HBsAg loss within 36 months of stopping antiviral treatment. The primary analysis was based on intention-to-treat allocation with last observation carried forward. Results: There was a numerical but not statistically significant difference in HBsAg loss between the low-threshold (3 of 64; 4.7%) and the high-threshold (8 of 63; 12.7%) group (risk difference: 8.0%, 95% CI: -2.3 to 19.6, p = 0.123). None of the patients with end-of-treatment HBsAg > 1000 IU/mL achieved HBsAg loss; among those with end-of-treatment HBsAg < 1000 IU/mL, 8 of 15 (53.3%) achieved HBsAg loss in the high-threshold group compared to 3 of 26 (11.5%) in the low-threshold group. Conclusions: We could not confirm our hypothesis that a higher threshold for restart of therapy after NA withdrawal improves the likelihood of HBsAg loss within 36 months in patients with HBeAg negative CHB. Further studies including only patients with HBsAg level <1000 IU/mL and/or larger sample size and longer follow-up duration are recommended.

• Mesinovic, Munib; Wong, Xin Ci; Rajahram, Giri Shan; Citarella, Barbara Wanjiru; Peariasamy, Kalaiarasu M. & Greve, Frank van Someren [Show all 1,671 contributors for this article] (2024). At-admission prediction of mortality and pulmonary embolism in an international cohort of hospitalised patients with COVID-19 using statistical and machine learning methods. Scientific Reports. 14(1). doi: 10.1038/s41598-024-63212-7. Full text in Research Archive
• Holmberg, Marte; Aass, Hans Christian; Dalgard, Olav; Samuelsen, Ellen; Sun, Dan & Björkström, Niklas K. [Show all 8 contributors for this article] (2023). Treatment cessation in HBeAg-negative chronic hepatitis B: clinical response is associated with increase in specific proinflammatory cytokines. Scientific Reports. 13(1). doi: 10.1038/s41598-023-50216-y. Full text in Research Archive Show summary

  Patients with HBeAg-negative chronic hepatitis B may experience an immune response after stopping nucleos(t)ide analogue (NA)therapy, which may potentially trigger HBsAg loss or off-therapy sustained viral control. The immunological mechanisms determining clinical response remain poorly understood. To identify inflammatory signatures associated with defined outcomes, we analysed plasma cytokines and chemokines from 57 HBeAg-negative patients enrolled in the Nuc-Stop Study at baseline and 12 weeks after NA cessation. Clinical response at 12 weeks was classified into four groups: immune control, viral relapse, evolving clinical relapse, and resolving clinical relapse. Twelve weeks after treatment cessation 17 patients (30%) experienced immune control, 19 (33%) viral relapse, 6 (11%) evolving clinical relapse, and 15 (26%) resolving clinical relapse. There was a significant increase in interferon-γ-induced protein 10 (IP-10; p = 0.012) and tumor necrosis factor (TNF; p = 0.032) in patients with evolving clinical relapse. Sparse partial least-squares multivariate analyses (sPLS-DA) showed higher first component values for the clinical relapse group compared to the other groups, separation was driven mainly by IP-10, TNF, IL-9, IFN-γ, MIP-1β, and IL-12. Our results demonstrate that evolving clinical relapse after NA cessation is associated with a systemic increase in the proinflammatory cytokines IP-10 and TNF.

• Gunst, Jesper D.; Højen, Jesper F.; Pahus, Marie H.; Rosás-Umbert, Miriam; Stiksrud, Birgitte & McMahon, James H. [Show all 33 contributors for this article] (2023). Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence: the randomized phase 2a TITAN trial. Nature Medicine. ISSN 1078-8956. 29(10), p. 2547–2558. doi: 10.1038/s41591-023-02547-6. Full text in Research Archive Show summary

  Inducing antiretroviral therapy (ART)-free virological control is a critical step toward a human immunodeficiency virus type 1 (HIV-1) cure. In this phase 2a, placebo-controlled, double-blinded trial, 43 people (85% males) with HIV-1 on ART were randomized to (1) placebo/placebo, (2) lefitolimod (TLR9 agonist)/placebo, (3) placebo/broadly neutralizing anti-HIV-1 antibodies (bNAbs) or (4) lefitolimod/bNAb. ART interruption (ATI) started at week 3. Lefitolimod was administered once weekly for the first 8 weeks, and bNAbs were administered twice, 1 d before and 3 weeks after ATI. The primary endpoint was time to loss of virologic control after ATI. The median delay in time to loss of virologic control compared to the placebo/placebo group was 0.5 weeks (P = 0.49), 12.5 weeks (P = 0.003) and 9.5 weeks (P = 0.004) in the lefitolimod/placebo, placebo/bNAb and lefitolimod/bNAb groups, respectively. Among secondary endpoints, viral doubling time was slower for bNAb groups compared to non-bNAb groups, and the interventions were overall safe. We observed no added benefit of lefitolimod. Despite subtherapeutic plasma bNAb levels, 36% (4/11) in the placebo/bNAb group compared to 0% (0/10) in the placebo/placebo group maintained virologic control after the 25-week ATI. Although immunotherapy with lefitolimod did not lead to ART-free HIV-1 control, bNAbs may be important components in future HIV-1 curative strategies. ClinicalTrials.gov identifier: NCT03837756.

• Tusch, Erich S.; Ryom, Lene; Fursa, Olga; Peters, Lars; Østergaard, Lars & Florence, Eric [Show all 22 contributors for this article] (2022). Incidence and risk factors for suicide, death due to substance use, and violent/accidental death in people with HIV. AIDS (London). ISSN 0269-9370. 37(1), p. 161–171. doi: 10.1097/QAD.0000000000003402. Full text in Research Archive
• Garcia-Gallo, Esteban; Merson, Laura; Kennon, Kalynn; Kelly, Sadie; Citarella, Barbara Wanjiru & Fryer, Daniel Vidali [Show all 1,775 contributors for this article] (2022). ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19. Scientific Data. 9(1). doi: 10.1038/s41597-022-01534-9. Full text in Research Archive Show summary

  The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use.

• Hole, Mikal Jacob; Jørgensen, Kristin Kaasen; Holm, Kristian; Braadland, Peder Rustøen; Meyer-Myklestad, Malin Holm & Medhus, Asle Wilhelm [Show all 13 contributors for this article] (2022). A shared mucosal gut microbiota signature in primary sclerosing cholangitis before and after liver transplantation. Hepatology. ISSN 0270-9139. doi: 10.1002/hep.32773. Full text in Research Archive Show summary

  Background and Aims Several characteristic features of the fecal microbiota have been described in primary sclerosing cholangitis (PSC), whereas data on mucosal microbiota are less consistent. We aimed to use a large colonoscopy cohort to investigate key knowledge gaps, including the role of gut microbiota in PSC with inflammatory bowel disease (IBD), the effect of liver transplantation (LT), and whether recurrent PSC (rPSC) may be used to define consistent microbiota features in PSC irrespective of LT. Approach and Results We included 84 PSC and 51 liver transplanted PSC patients (PSC-LT) and 40 healthy controls (HCs) and performed sequencing of the 16S ribosomal RNA gene (V3–V4) from ileocolonic biopsies. Intraindividual microbial diversity was reduced in both PSC and PSC-LT versus HCs. An expansion of Proteobacteria was more pronounced in PSC-LT (up to 19% relative abundance) than in PSC (up to 11%) and HCs (up to 8%; QFDR < 0.05). When investigating PSC before (PSC vs. HC) and after LT (rPSC vs. no-rPSC), increased variability (dispersion) in the PSC group was found. Five genera were associated with PSC before and after LT. A dysbiosis index calculated from the five genera, and the presence of the potential pathobiont, Klebsiella, were associated with reduced LT-free survival. Concomitant IBD was associated with reduced Akkermansia. Conclusions Consistent mucosal microbiota features associated with PSC, PSC-IBD, and disease severity, irrespective of LT status, highlight the usefulness of investigating PSC and rPSC in parallel, and suggest that the impact of gut microbiota on posttransplant liver health should be investigated further.

• Nikolaichuk, Myroslava; Mocroft, Amanda; Wandeler, Gilles; Szlavik, János; Gottfredsson, Magnus & Reikvam, Dag Henrik [Show all 21 contributors for this article] (2022). Use of contraindicated antiretroviral drugs in people with HIV/HCV coinfections receiving HCV treatment with direct-acting antivirals—Results from the EuroSIDA study. HIV Medicine. ISSN 1464-2662. doi: 10.1111/hiv.13357. Full text in Research Archive Show summary

  Objectives Our objective was to determine whether antiretroviral drugs (ARVs) were used according to the European AIDS Clinical Society (EACS) guidelines for people with HIV/hepatitis C virus (HCV) coinfection treated with direct-acting antivirals (DAAs) between 30 November 2014 and 31 December 2019 in the pan-European EuroSIDA study. Methods At each publication date of the EACS guidelines, plus 3 and 6 months, we calculated the number of people receiving DAAs with potential and actual ARV contraindications (‘red shading’ in the EACS guidelines). We used logistic regression to investigate factors associated with using contraindicated ARVs. Results Among 1406 people starting DAAs, the median age was 51 years, 75% were male, 57% reported injected drug use as an HIV risk, and 76% were from western Europe. Of 1624 treatment episodes, 609 (37.5%) occurred while the patient was receiving ARVs with potential contraindications; among them, 38 (6.2%; 95% confidence interval [CI] 4.3–8.2) involved a contraindicated ARV (18 non-nucleoside reverse transcriptase inhibitors), 16 involved protease inhibitors, and four involved integrase strand transfer inhibitors. The adjusted odds of receiving a contraindicated ARV were higher (3.25; 95% CI 1.40–7.57) among participants from east/central east Europe (vs. south) and lower (0.22; 95% CI 0.08–0.65) for 2015–2018 guidelines (vs. 2014). In total, 29 of the 32 (90.6%) patients receiving a contraindicated ARV and 441 of the 461 (95.7%) with potential ARV contraindications experienced a sustained virological response ≥12 weeks after stopping treatment (SVR12; p = 0.55). Conclusion In this large heterogenous European cohort, more than one-third of people with HIV/HCV coinfection received DAAs with potential ARV contraindications, but few received a contraindicated ARV. Use of contraindicated ARVs declined over time, corresponding to the increased availability of ARV therapy regimens without interactions with DAA across Europe. Participants who received a contraindicated DAA and ARV combination still had a high rate of SVR12.

• Bouziotis, Jason; Arvanitakis, Marianna; Preiser, Jean-Charles; Abbas, Ali; Abdukahil, Sheryl Ann & Abdulkadir, Nurul Najmee [Show all 50 contributors for this article] (2022). Association of body mass index with COVID-19 related in-hospital death. Clinical Nutrition. ISSN 0261-5614. 41(12), p. 2924–2926. doi: 10.1016/j.clnu.2022.01.017. Full text in Research Archive Show summary

  Background: Patients with extreme body mass indices (BMI) could have an increased risk of death while hospitalized for COVID-19.<p> <p>Methods: The database of the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) was used to assess the time to in-hospital death with competing-risks regression by sex and between the categories of BMI. <p>Results: Data from 12,137 patients (age 60.0 ± 16.2 years, 59% males, BMI 29.4 ± 6.9 kg/m² ) of 48 countries were available. By univariate analysis, underweight patients had a higher risk of mortality than the other patients (sub-hazard ratio (SHR) 1.75 [1.44e2.14]). Mortality was lower in normal (SHR 0.69 [0.58e0.85]), overweight (SHR 0.53 [0.43e0.65]) and obese (SHR 0.55 [0.44e0.67]) than in underweight patients. Multivariable analysis (adjusted for age, chronic pulmonary disease, malignant neoplasia, type 2 diabetes) confirmed that in-hospital mortality of underweight patients was higher than overweight patients (females: SHR 0.63 [0.45e0.88] and males: 0.69 [0.51e0.94]). <p>Conclusion: Even though these findings do not imply changes in the medical care of hospitalized patients, they support the use of BMI category for the stratification of patients enrolled in interventional studies where mortality is recorded as an outcome.

• Meyer-Myklestad, Malin Holm; Medhus, Asle Wilhelm; Stiksrud, Birgitte; Lorvik, Kristina Berg; Seljeflot, Ingebjørg & Hansen, Simen Hyll [Show all 13 contributors for this article] (2022). Probiotics to HIV-infected immunological nonresponders: Altered mucosal immunity and microbial diversity restricted to ileum. Journal of Acquired Immune Deficiency Syndromes. ISSN 1525-4135. 89(1), p. 77–86. doi: 10.1097/QAI.0000000000002817. Full text in Research Archive
• Cho, Sung-Min; White, Nicole; Premraj, Lavienraj; Battaglini, Denise; Fanning, Jonathon & Suen, Jacky [Show all 50 contributors for this article] (2022). Neurological manifestations of COVID-19 in adults and children. Brain. ISSN 0006-8950. doi: 10.1093/brain/awac332. Full text in Research Archive
• Gonçalves, Bronner P.; Hall, Matthew; Jassat, Waasila; Balan, Valeria; Murthy, Srinivas & Kartsonaki, Christiana [Show all 50 contributors for this article] (2022). An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients. eLIFE. 11. doi: 10.7554/eLife.80556. Full text in Research Archive
• Reyes, Luis Felipe; Murthy, Srinivas; Garcia-Gallo, Esteban; Merson, Laura; Ibáñez-Prada, Elsa D. & Rello, Jordi [Show all 51 contributors for this article] (2022). Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study. Critical Care. ISSN 1364-8535. 26(1). doi: 10.1186/s13054-022-04155-1. Full text in Research Archive
• Wainstein, Marina; MacDonald, Samual; Fryer, Daniel; Young, Kyle; Balan, Valeria & Begum, Husna [Show all 50 contributors for this article] (2022). Use of an extended KDIGO definition to diagnose acute kidney injury in patients with COVID-19: A multinational study using the ISARIC–WHO clinical characterisation protocol. PLoS Medicine. ISSN 1549-1277. 19(4). doi: 10.1371/journal.pmed.1003969. Full text in Research Archive
• Lorvik, Kristina Berg; Meyer-Myklestad, Malin Holm; Kushekhar, Kushi; Handeland, Charlotte Andrea; Medhus, Asle Wilhelm & Lund-Iversen, Marius [Show all 11 contributors for this article] (2021). Enhanced Gut-Homing Dynamics and Pronounced Exhaustion of Mucosal and Blood CD4⁺ T Cells in HIV-Infected Immunological Non-Responders. Frontiers in Immunology. 12, p. 1–12. doi: 10.3389/fimmu.2021.744155. Full text in Research Archive Show summary

  Immunological non-responders (INR), a subgroup of people living with HIV (PLHIV) who fail to restore CD4 + T cell numbers upon effective antiretroviral treatment, have impaired gut mucosal barrier function and an inferior clinical prognosis compared with immunological responders (IR). The contribution of gut-homing and exhaustion of mucosal T cells to the INR phenotype was previously unknown. Flow cytometry analysis of mononuclear cells from peripheral blood and ileal and colonic lamina propria showed that INR had higher fractions of gut-homing CD4 + T cells in blood compared with IR. In addition, gut-homing cells were more likely to display signs of exhaustion in INR. The increased CD4 + T cell exhaustion in INR was ubiquitous and not restricted to subpopulations defined by activation, differentiation or regulatory T cell markers. In INR, colon CD4 + T cell exhaustion correlated negatively with the fraction of CD4 + T cells in the same compartment, this was not apparent in the ileum. The fraction of exhausted mucosal CD4 + T cells correlated with I-FABP and REG3α, markers of enterocyte damage. We conclude that alterations of gut-homing and exhaustion of T cells may contribute to impaired gut immune and barrier functions associated with immunological non-response in PLHIV.

• Pelchen-Matthews, Annegret; Borges, Álvaro H.; Reekie, Joanne; Rasmussen, Line D.; Wiese, Lothar & Weber, Jonathan [Show all 183 contributors for this article] (2021). Prevalence and Outcomes for Heavily Treatment-Experienced Individuals Living With Human Immunodeficiency Virus in a European Cohort. Journal of Acquired Immune Deficiency Syndromes. ISSN 1525-4135. 87(2), p. 806–817. doi: 10.1097/QAI.0000000000002635. Full text in Research Archive
• Pedersen, Hallvard Berge; Kaviyani, Robin Sviggum; Paulsen, Else Quist; Dedi, Lumnije; Reikvam, Dag Henrik & Jenum, Synne [Show all 9 contributors for this article] (2021). En mann i 70-årene med pleuravæske, knesmerter og dysartri etter åpen hjertekirurgi. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 141(18). doi: 10.4045/tidsskr.21.0163. Full text in Research Archive
• Abdukahil, Sheryl Ann; Abe, Ryuzo; Abel, Laurent; Absil, Lara; Acharya, Subhash & Acker, Andrew [Show all 50 contributors for this article] (2021). Ten months of temporal variation in the clinical journey of hospitalised patients with COVID-19: An observational cohort. eLIFE. 10:e70970, p. 1–30. doi: 10.7554/eLife.70970. Full text in Research Archive Show summary

  Background: There is potentially considerable variation in the nature and duration of the care provided to hospitalised patients during an infectious disease epidemic or pandemic. Improvements in care and clinician confidence may shorten the time spent as an inpatient, or the need for admission to an intensive care unit (ICU) or high dependency unit (HDU). On the other hand, limited resources at times of high demand may lead to rationing. Nevertheless, these variables may be used as static proxies for disease severity, as outcome measures for trials, and to inform planning and logistics. Methods: We investigate these time trends in an extremely large international cohort of 142,540 patients hospitalised with COVID-19. Investigated are: time from symptom onset to hospital admission, probability of ICU/HDU admission, time from hospital admission to ICU/HDU admission, hospital case fatality ratio (hCFR) and total length of hospital stay. Results: Time from onset to admission showed a rapid decline during the first months of the pandemic followed by peaks during August/September and December 2020. ICU/HDU admission was more frequent from June to August. The hCFR was lowest from June to August. Raw numbers for overall hospital stay showed little variation, but there is clear decline in time to discharge for ICU/HDU survivors. Conclusions: Our results establish that variables of these kinds have limitations when used as outcome measures in a rapidly evolving situation. Funding: This work was supported by the UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z] and the Bill & Melinda Gates Foundation [OPP1209135]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

• Reyes, Luis Felipe; Murthy, Srinivas; Garcia-Gallo, Esteban; Irvine, Mike; Merson, Laura & Martin-Loeches, Ignacio [Show all 50 contributors for this article] (2021). Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the ISARIC WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study. European Respiratory Journal Open Research (ERJ Open Research). 8(1). doi: 10.1183/23120541.00552-2021. Full text in Research Archive Show summary

  Due to the large number of patients with severe coronavirus disease 2019 (COVID-19), many were treated outside the traditional walls of the intensive care unit (ICU), and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the International Severe Acute Respiratory and Emerging Infection Consortium World Health Organization COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or noninvasive mechanical ventilation, high-flow nasal cannula, inotropes or vasopressors. A logistic generalised additive model was used to compare clinical outcomes among patients admitted or not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median (interquartile range (IQR), 67 (55–78) years), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 (5–19) days and was longer in patients admitted to an ICU than in those who were cared for outside the ICU (12 (6–23) days versus 8 (4–15) days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% (5797 out of 18 831) versus 39.0% (7532 out of 19 295), p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR 0.70, 95% CI 0.65–0.75; p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside an ICU.

• Hoel, Hedda Benedicte; Heggelund, Lars; Reikvam, Dag Henrik; Stiksrud, Birgitte; Ueland, Thor & Michelsen, Annika [Show all 15 contributors for this article] (2020). Elevated markers of gut leakage and inflammasome activation in COVID-19 patients with cardiac involvement. Journal of Internal Medicine. ISSN 0954-6820. 289(4). doi: 10.1111/joim.13178. Full text in Research Archive Show summary

  Background A high proportion of COVID‐19 patients have cardiac involvement, even those without known cardiac disease. Downregulation of angiotensin converting enzyme 2 (ACE2), a receptor for SARS‐CoV‐2 and the renin‐angiotensin system, as well as inflammatory mechanisms have been suggested to play a role. ACE2 is abundant in the gut and associated with gut microbiota composition. We hypothesized that gut leakage of microbial products, and subsequent inflammasome activation could contribute to cardiac involvement in COVID‐19 patients. Methods Plasma levels of a gut leakage marker (LPS‐binding protein, LBP), a marker of enterocyte damage (intestinal fatty acid binding protein, IFABP), a gut homing marker (CCL25, ligand for chemokine receptor CCR9) and markers of inflammasome activation (IL‐1β, IL‐18 and their regulatory proteins) were measured at three time points (day 1, 3–5 and 7–10) in 39 hospitalized COVID‐19 patients and related to cardiac involvement. Results Compared to controls, COVID‐19 patients had elevated plasma levels of LBP and CCL25 but not IFABP, suggesting impaired gut barrier function and accentuated gut homing of T cells without excessive enterocyte damage. Levels of LBP were twice as high at baseline in patients with elevated cardiac markers compared with those without and remained elevated during hospitalization. Also, markers of inflammasome activation were moderately elevated in patients with cardiac involvement. LBP was associated with higher NT‐pro‐BNP levels, whereas IL‐18, IL‐18BP and IL‐1Ra were associated with higher troponin levels. Conclusion Patients with cardiac involvement had elevated markers of gut leakage and inflammasome activation, suggestive of a potential gut‐heart axis in COVID‐19.

• Meyer-Myklestad, Malin Holm; Medhus, Asle Wilhelm; Lorvik, Kristina Berg; Seljeflot, Ingebjørg; Hansen, Simen Hyll & Holm, Kristian [Show all 13 contributors for this article] (2020). HIV-infected immunological non-responders have colon-restricted gut mucosal immune dysfunction. Journal of Infectious Diseases. ISSN 0022-1899. doi: 10.1093/infdis/jiaa714. Full text in Research Archive Show summary

  Abstract Background Human immunodeficiency virus (HIV)–infected immunological nonresponders (INRs) fail to reconstitute their CD4+ T-cell pool after initiation of antiretroviral therapy, and their prognosis is inferior to that of immunological responders (IRs). A prevailing hypothesis is that the INR phenotype is caused by a persistently disrupted mucosal barrier, but assessments of gut mucosal immunology in different anatomical compartments are scarce. Methods We investigated circulating markers of mucosal dysfunction, immune activation, mucosal Th17 and Th22 cells, and mucosa-adherent microbiota signatures in gut mucosal specimens from sigmoid colon and terminal ileum of 19 INRs and 20 IRs in addition to 20 HIV-negative individuals. Results INRs had higher blood levels of the enterocyte damage marker intestinal fatty acid–binding protein than IRs. In gut mucosal biopsies, INRs had lower fractions of CD4+ T cells, higher fractions of interleukin 22, and a tendency to higher fractions of interleukin 17–producing CD4+ T cells. These findings were all restricted to the colon and correlated to circulating markers of enterocyte damage. There were no observed differences in gut microbial composition between INRs and IRs. Conclusions Restricted to the colon, enterocyte damage and mucosal immune dysfunction play a role for insufficient immune reconstitution in HIV infection independent of the gut microbiota.

• Reikvam, Dag Henrik; Meyer-Myklestad, Malin Holm; Trøseid, Marius & Stiksrud, Birgitte (2020). Probiotics to manage inflammation in HIV infection. Current Opinion in Infectious Diseases. ISSN 0951-7375. 33(1), p. 34–43. doi: 10.1097/QCO.0000000000000612. Full text in Research Archive
• Pelchen-Matthwes, Annegret; Ryom, Lene; Borges, Alvaro H; Edwards, Simon; Duvivier, Claudine & Stephan, Cristoph [Show all 22 contributors for this article] (2018). Aging and the evolution of comorbidities among HIV-positive individuals in a European cohort. AIDS (London). ISSN 0269-9370. 32(16), p. 2405–2416. doi: 10.1097/QAD.0000000000001967. Full text in Research Archive
• Bråten, Lars Christian Haugli & Reikvam, Dag Henrik (2016). Noe å lære av: En mann i 30-årene med feber etter safari i Sør-Afrika. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 136(4), p. 328–330. Full text in Research Archive
• Hesstvedt, Liv; Reikvam, Dag Henrik & Dunlop, Oona Borghild (2015). Neurological melioidosis in Norway presenting with a cerebral abscess. IDCases. 2(1), p. 16–18. doi: 10.1016/j.idcr.2014.11.001. Full text in Research Archive
• Reikvam, Dag Henrik; Derrien, Muriel; Islam, Rejoanoul; Erofeev, Alexander; Grcic, Vedrana & Sandvik, Anders [Show all 11 contributors for this article] (2012). Epithelial-microbial crosstalk in polymeric Ig receptor deficient mice. European Journal of Immunology. ISSN 0014-2980. 42(11), p. 2959–2970. doi: 10.1002/eji.201242543. Full text in Research Archive
• Reikvam, Dag Henrik; Perminow, Gøri Margrete; Lyckander, Lars Gustav; Gran, Jon Michael; Brandtzæg, Per & Vatn, Morten [Show all 7 contributors for this article] (2011). Increase of regulatory T cells in ileal mucosa of untreated pediatric Crohn's disease patients. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 46(5), p. 550–560. doi: 10.3109/00365521.2011.551887. Full text in Research Archive
• Reikvam, Dag Henrik; Erofeev, Alexander; Sandvik, Anders; Grcic, Vedrana; Jahnsen, Frode Lars & Gaustad, Peter [Show all 10 contributors for this article] (2011). Depletion of Murine Intestinal Microbiota: Effects on Gut Mucosa and Epithelial Gene Expression. PLOS ONE. 6(3). doi: 10.1371/journal.pone.0017996. Full text in Research Archive
• Finanger, Gøri Margrete; Reikvam, Dag Henrik; Lyckander, LG; Brandtzæg, Per; Vatn, Morten H & Carlsen, Hege Synnøve (2009). Increased Number and Activation of Colonic Macrophages in Pediatric Patients with Untreated Crohn's Disease. Inflammatory Bowel Diseases. ISSN 1078-0998. 15(9), p. 1368–1378. doi: 10.1002/ibd.20916. Full text in Research Archive

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• Johannessen, Asgeir; Reikvam, Dag Henrik & Dalgard, Olav (2024). Letter: Should HBV Therapy Be Stopped Based on HBsAg Level Alone? Authors' Reply. Alimentary Pharmacology and Therapeutics. ISSN 0269-2813. 61(2), p. 404–405. doi: 10.1111/apt.18439. Full text in Research Archive
• Hole, Mikal Jacob; Jørgensen, Kristin Kaasen; Holm, Kristian; Braadland, Peder Rustøen; Meyer-Myklestad, Malin Holm & Medhus, Asle Wilhelm [Show all 13 contributors for this article] (2023). Reply: The mucosal gut signature in primary sclerosing cholangitis before and after liver transplantation. Is the dysbiosis index really predictive for the recurrence of PSC? Hepatology. ISSN 0270-9139. 77(6), p. E188–E189. doi: 10.1097/HEP.0000000000000340. Full text in Research Archive
• Meyer-Myklestad, Malin Holm; Kummen, Martin; Stiksrud, Birgitte; Holm, Kristian; Dyrhol-Riise, Anne Ma & Kvale, Dag [Show all 11 contributors for this article] (2019). ALTERED GUT IMMUNITY IN IMMUNOLOGICAL NONRESPONDERS PARTLY RESTORED BY PROBIOTICS. Full text in Research Archive
• Reikvam, Dag Henrik (2019). Immunforsvaret i tarmen. Full text in Research Archive
• Lorvik, Kristina Berg; Meyer-Myklestad, Malin Holm; Medhus, Asle Wilhelm; Kvale, Dag; Dyrhol-Riise, Anne Ma & Reikvam, Dag Henrik [Show all 7 contributors for this article] (2019). Increased expression of gut and blood CD4+ T cells in people living with HIV and insufficient response to antiviral therapy. Full text in Research Archive
• Grcic, Vedrana; Sandvik, Anders; Reikvam, Dag Henrik; Jahnsen, Frode Lars & Johansen, Finn Eirik (2010). Ectopic Expression of Cryptdins in Colon of Mice Lacking Secretory Immunoglobulins. Full text in Research Archive
• Sandvik, Anders; Grzyb, Krzysztof; Reikvam, Dag Henrik; Erofeev, Alexander; Bækkevold, Espen Sønderaal & Jahnsen, Frode Lars [Show all 7 contributors for this article] (2009). Oral treatment with soluble beta-glucan protects against experimental ulcerative colitis. Full text in Research Archive
• Erofeev, Alexander; Reikvam, Dag Henrik; Gaustad, Peter; Grzyb, Krzysztof; Sandvik, Anders & Jahnsen, Frode Lars [Show all 7 contributors for this article] (2009). Role of secretory antibodies and commensal microbiota in DSS-induced colitis. Full text in Research Archive
• Sandvik, Anders; Grzyb, Krzysztof; Reikvam, Dag Henrik; Erofeev, Alexander; Bækkevold, Espen Sønderaal & Jahnsen, Frode Lars [Show all 7 contributors for this article] (2009). Oral treatment with soluble beta-glucan protects against experimental ulcerative colitis. Full text in Research Archive
• Kran, Anne-Marte Bakken; Håvelsrud, Othilde Elise; Storm, Margrethe Larsdatter; Blix, Hege Salvesen; Bragstad, Karoline & Stene-Johansen, Kathrine [Show all 15 contributors for this article] (2023). Usage of Antivirals and the Occurrence of Antiviral Resistance in Norway 2022. RAVN. Folkehelseinstituttet. ISSN 9788284064017. Full text in Research Archive
• Kran, Anne-Marte Bakken; Storm, Margrethe Larsdatter; Håvelsrud, Othilde Elise; Litleskare, Irene; Bragstad, Karoline & Stene-Johansen, Kathrine [Show all 14 contributors for this article] (2022). Usage of Antivirals and the Occurrence of Antiviral Resistance in Norway 2021. RAVN. Norwegian Institute of Public Health, Division of Infection Control. ISSN 9788284063225. Full text in Research Archive Show summary

  The usage of antivirals According to The Norwegian Drug Wholesales Statistics Database, the sales of antiviral drugs measured in defined daily doses (DDDs) were reduced in 2021, after several years of increase. This reduction was primarily due to a small decrease in sales of antivirals against HIV, which make up a large proportion of the antiviral drugs sold in Norway. There was no decrease in the number of people being treated with HIV drugs compared to previous years, but as a growing proportion of patients is treated with single tablet regimens, the number of drugs sold is reduced. When looking at the number of persons treated with antiviral drugs, the antiviral treatment received by the highest number of patients are drugs used against herpes viruses. In 2021, the sale of antivirals against herpes virus, especially valaciclovir, increased even further. There was a decrease in the sales of agents against hepatitis C and influenza, while treatments for hepatitis B were unchanged. Influenza virus Similar to the previous influenza season, the season of 2021/2022 was also unusual, mainly due to the infection control measures implemented in response to the pandemic. There was a very low incidence of influenza at the beginning of the season, followed by a short period with significant spread of infection during the spring of 2021. No drug resistance against neuraminidase inhibitors was detected, but a mutation conferring resistance to the new drug baloxavir marboxil was found in one sample. Human immunodeficiency virus-1 The decreasing trend in the number of new HIV-infections has continued in 2021, which is also reflected in a reduction in the number of samples received for surveillance of primary drug resistance. A total of 64 samples were analysed as part of the surveillance in 2021, and only 13 of these were from patients infected in Norway. For the first time, we have been able to classify cases according to site of residence at the time of infection. Among those living in Norway at the time of infection, as much as 88% of the cases reported to MSIS were also reported to RAVN. This indicates that national routines for follow-up of newly diagnosed patients with regard to antiviral resistance are good. Resistance mutations were detected in 11% of the examined samples, which is comparable to previous years. In 2021, only mutations affecting reverse transcriptase inhibitors and none affecting protease inhibitors were found. Hepatitis B virus In 2021, a total of 134 samples with hepatitis B virus (HBV) were analysed for resistance mutations. Most of these samples (n=117) had been submitted to the reference laboratory for genotyping prior to treatment. These samples constitute the Norwegian surveillance of primary resistance. The remaining 17 samples were from patients with ongoing antiviral treatment and were submitted for investigation of resistance as a possible cause of treatment failure. Relevant resistance mutations were found in five of the 17 samples from patients with treatment failure. No resistance mutations were found in any of the surveillance samples. Human herpes viruses: Cytomegalovirus In 2021, 19 samples were submitted for resistance testing at the reference laboratory for cytomegalovirus (CMV). Relevant resistance mutations were detected in five of these samples. Low or moderate resistance to ganciclovir was found in four of these samples, while moderate resistance to the new drug maribavir was found in one sample. There is no systematic surveillance of resistance in CMV, and the true incidence of drug resistance cannot be determined. Human herpes viruses: Herpes simplex virus In 2021, only five samples with herpes simplex virus (HSV) were analysed for resistance. Two of the samples had mutations conferring resistance to aciclovir. Despite an increase in the use of aciclovir both as treatment and prophylaxis, samples are rarely submitted for resistance testing. Like CMV, there is no systematic surveillance of HSV drug resistance. Hepatitis C virus A systematic surveillance system for newly diagnosed HCV infections was launched in May 2022. In 2021, resistance testing was performed on a limited number of samples submitted for resistance testing. Drug resistance data is cross-referenced with epidemiological data from MSIS to enable comparisons of different subgroups. Resistance associated substitutions were detected in seven out of eight samples analysed for resistance, two of which were from treatment experienced patients, one sample was from a patient with no previous treatment exposure and the remaining four were from patients where treatment exposure was not known. SARS-CoV-2 Surveillance of antiviral resistance in SARS-CoV-2 has not been collected to RAVN in 2021. Oral drugs for the treatment of COVID-19 will be available in Norway from the autumn of 2022, and a system for surveillance of antiviral resistance will probably be implemented from the beginning of 2023. This surveillance will be based on the same sequence data that is part of the national monitoring of variants.

• Reikvam, Dag Henrik & Johansen, Finn-Eirik (2011). Mucosal homeostasis and inflammatory bowel disease. Universitetet i Oslo. Full text in Research Archive
• Johansen, Finn Eirik; Sandvik, Anders; Grcic, Vedrana & Reikvam, Dag Henrik (2010). Ectopic expression of cryptdins in colon of mice lacking secretory immunoglobulins. Universitetet i Oslo. Full text in Research Archive

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