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Background: Anifrolumab, a monoclonal antibody targeting the type 1 interferon (IFN-I) signaling pathway, holds promise as a therapeutic intervention for systemic lupus erythematosus (SLE). However, its use is associated with an increased risk of infections, particularly viral infections like herpes zoster (HZ). Results from the clinical trials on anifrolumab show yearly rates of upper respiratory tract infections of 34% and HZ of 6.1%. An increased frequency of other specific viral infections, including herpes simplex virus (HSV), was not reported. Case Reports: Here, we present 2 cases of patients with SLE treated with anifrolumab, both experiencing severe adverse reactions in the form of disseminated herpesvirus infections, specifically disseminated HSV-2 and varicella zoster virus (VZV, HZ encephalitis). To the best of our knowledge, no previous reports of severe disseminated HSV-2 or HZ have been published in anifrolumab-treated patients. The patient in case 1 experienced a primary HSV-2 infection following anifrolumab treatment, potentially explaining the severity of the infection. The patient in case 2 had a history of previous HZ skin infections, which may have increased her risk of disseminated infection. Both patients recovered from the infections with minor sequelae, but they still require prophylactic antiviral treatment. These cases highlight the critical role of IFN-I immunity in protecting against herpesvirus infections. Conclusions: Thorough risk assessment before anifrolumab initiation, considering the patient's viral infection history, vaccination status, and potential exposure risks, is essential. Administration of recombinant zoster vaccine before anifrolumab therapy may benefit susceptible individuals. [ABSTRACT FROM AUTHOR]

This case report discusses a patient with systemic lupus erythematosus (SLE) treated with low-dose azathioprine who developed progressive multifocal leukoencephalopathy (PML). PML is a rare, severe, demyelinating disease linked to John Cunningham polyomavirus (JCV) reactivation. Treated with pembrolizumab, an immune checkpoint inhibitor, the patient initially improved. However, after the fourth dose, her condition rapidly worsened resulting in treatment discontinuation and death. Similar cases highlight the complex interplay of factors in PML development in SLE patients, including immunosuppression and genetic factors. The use of pembrolizumab in PML and SLE necessitates careful consideration of potential complications. [ABSTRACT FROM AUTHOR]

Problem The introduction of antiretroviral therapy (ART) for HIV infection in sub-Saharan Africa has improved the quality of life of millions of people and reduced mortality. However, substantial problems with the infrastructure for ART delivery remain. Approach Clinicians and researchers at an HIV clinic in Guinea-Bissau identified problems with the delivery of ART by establishing a clinical database and by collaborating with international researchers. Local setting The Bissau HIV cohort study group was established in 2007 as a collaboration between local HIV physicians and international HIV researchers. Patients were recruited from the HIV clinic at the country's main hospital in the capital Bissau. Relevant changes Between 2005 and 2013, 5514 HIV-positive patients were treated at the clinic. Working together, local health-care workers and international researchers identified the main problems affecting ART delivery: inadequate drug supply; loss of patients to follow-up; and inadequate laboratory services. Solutions to these problems were devised. The collaborations encouraged local physicians to start their own research projects to find possible solutions to problems at the clinic. Lessons learnt The HIV clinic in Bissau faced numerous obstacles in delivering ART at a sufficiently high quality and patients' lives were put in jeopardy. The effectiveness of ART could be enhanced by delivering it as part of an International research collaboration since such collaborations can help identify problems, find solutions and increase the capacity of the health-care system. Probleme L'introduction de la therapie antiretrovirale (TAR) pourtraiter la contamination par le VIH en Afrique subsaharienne a ameliore la qualite de vie de millions de personnes et redult la mortalite. Cependant, l'infrastructure de distribution de la TAR reste tres problematique. Approche Les cliniciens et les chercheurs d'une clinique de Guinee Bissau ont identifie des problemes avec la distribution de la IAK en creant une base de donnees clinique et en collaborant avec des chercheurs internatlonaux. Environnement local Le groupe d'etude de la cohorte VIH de Bissau a ete cree en 2007 comme une collaboration entre des medecins locaux traitant le VIH et des chercheurs internationaux etudlant le VIH. Les patients ont ete recrutesa la clinique VIH situee dans l'hopital principal du pays a Bissau, la capitale. Changements significatifs Entre 2005 et 2013, 5514 patients seropositifs ont ete traites a la clinique. En travaillant ensemble, les personnels de sante locaux et les chercheurs internationaux ont identifie les problemes principaux qui affectaient la distribution de la TAR: un approvisionnement inapproprie des medicaments; des patients perdus de vue et des services de laboratoire inadequats. Des solutions visant a resoudre ces problemes ont ete envisagees. Les collaborations ont encourage les medecins locaux a lancer leurs propres projets de recherche afin de trouver des solutions possibles aux problemes rencontres a la clinique. Lecons tirees La clinique VIH de Bissau a du faire face a de nombreux obstacles pour distrlbuer une TAR d'une qualite suffisamment elevee, et les vies des patients ont ete mises en peril. Lefficacite de la TAR pourrait etre augmentee en la distribuant dans le cadre de collaborations de recherche Internationale, puisque ces collaborations peuvent aider a identifier les problemes, a trouver des solutions et a augmenter la capacite du systeme de sante. Situacion La introduccion de la terapia antirretroviral (TARV) para tratar la Infeccion del VIH en el Africa subsahariana ha mejorado la calidad de vida de millones de personas y ha reducido la mortalidad. No obstante, siguen existiendo problemas considerables relacionados con la infraestructura para el suministro de la terapia antirretroviral. Enfoque En una clinica del VIH de Guinea-Bissau, los medicos y los investigadores detectaron problemas en el suministro de la terapia antirretroviral mediante la creacion de una base de datos y la colaboracion con investigadores internacionales. Marco regional El grupo del estudio de cohorte para el VIH de Bissau se creo en 2007, fruto de la colaboracion entre los medicos del VIH locales y los Investigadores del VIH Internacionales. Se selecciono a los pacientes de la clinica de VIH en el hospital principal del pais de la capital Bissau. Cambios importantes Entre 2005 y 2013, se trato a 5514 pacientes seropositivos para el VIH en la clinica. Trabajando en equipo, el personal sanitario local y los investigadores internacionales Identificaron los problemas principales que repercuten en el suministro de la terapia antirretroviral: el suministro inadecuado de medicamentos; la perdida de pacientes durante el seguimiento y los servicios de laboratorio inadecuados. Se disenaron soluciones para estos problemas. Las colaboraciones animaron a los medicos locales a emprender sus propios proyectos de investigacion a fin de hallar soluciones a los problemas en la clinica. Lecciones aprendidas La clinica del VIH de Bissau afronto diversos obstaculos en el suministro de una terapia antirretroviral de calidad suficientemente alta y se pusieron en riesgo las vidas de los pacientes. Es posible aumentar la eficacia de la terapia antirretroviral si esta se suministra como parte de la colaboracion de una investigacion internacional, ya que este tipo de colaboraciones pueden ayudar a Identificar los problemas, hallar soluciones y aumentar la capacidad del sistema sanitario., Introduction In sub-Saharan Africa, the introduction of antiretroviral therapy (ART) for patients with human immunodeficiency virus (HIV) infections has improved the lives of millions of people and decreased mortality. (1) [...]

Preliminary data on HIV-positive donor to HIV-positive recipient kidney transplantation suggest promising patient outcomes without adverse events. This is an important step in expanding the donor pool and opportunity for transplantation in HIV-positive patients. We herein report the first case of HIV-positive donor to HIV-positive recipient kidney transplantation in Denmark. Our patient has demonstrated a successful post-transplant course with excellent 1-year graft function, no rejection episodes, good virological control with undetectable HIV RNA, no signs of HIV-associated nephropathy, and no superinfections or opportunistic infections. This case corroborates findings from previous studies showing that kidney transplantation from carefully selected HIV-infected donors to carefully selected HIV-infected recipients seems to be a safe and effective treatment option, and supports the opportunity to expand the organ donor pool for this group of patients with end-stage renal disease. [ABSTRACT FROM AUTHOR]

The study aimed to determine adjusted all‐cause mortality and cause of death in persons with chronic hepatitis B virus (HBV) infection compared with age‐ and sex‐matched persons from the general population. We used nationwide registers to identify persons aged ≥18 years with chronic HBV infection in 2002–2017 in Denmark and included 10 age‐ and sex‐matched controls for each. Follow‐up was from 6 months after diagnosis until death, emigration, or 31 December 2017. Mortality rate ratios (MRRs) adjusted for age, sex, employment, origin and comorbidity were calculated using Poisson regression. Unadjusted cause‐specific mortality rate ratios with 95% confidence intervals were calculated assuming a Poisson distribution. A total of 6988 persons with chronic HBV infection and 69,847 controls were included. During a median follow‐up of 7.7 years (range 0.0–15.5), 315 (5%) persons with—and 1525 (2%) without—chronic HBV infection died. The adjusted all‐cause MRR was 1.5 (95% CI 1.2–2.0). Persons with chronic HBV infection had increased mortality due to liver disease including hepatocellular carcinoma (MRR 12.3 [8.6–17.7]), external causes (MRR 3.3 [2.5–4.7]), endocrine disease (MRR 3.2 [1.8–5.4]), genitourinary disease (MRR 3.2 [1.2–7.6]) and neoplasms (except hepatocellular carcinoma; MRR 1.6 [1.2–2.0]). In conclusion, this study showed an increased all‐cause mortality in persons with chronic HBV infection in comparison with age‐ and sex‐matched persons without chronic HBV infection which remained after adjustment for several confounding factors. Excess mortality was mainly associated with liver disease, but also external factors, endocrine disease, genitourinary disease and neoplasms (excluding hepatocellular carcinoma). [ABSTRACT FROM AUTHOR]

As partner notification (PN) has shown effective in increasing the number of partners of HIV infected patients being tested we aimed to evaluate the feasibility of implementing PN in the West-African country Guinea-Bissau. Patients enrolled were offered the choice of three different PN methods. Acceptance, successful referrals and HIV status of partners were evaluated. Of 697 patients offered PN, 495 (71.0%) accepted and listed 547 partners. At end of follow-up 118 (21.5%) partners had been tested of which 44 (37.3%) were HIV infected. HIV infected partners had a higher median CD4 count at diagnosis compared with index patients; 401 cells/mm3 versus 240 cells/mm3, p < 0.001. The results indicate that implementation of PN is feasible, effective in identifying HIV infected partners and enables initiation of earlier treatment, yet there are major barriers to bringing partners in for testing which should be addressed in order to exploit the full potential of PN. [ABSTRACT FROM AUTHOR]

Introduction: With more people receiving antiretroviral treatment (ART), the need to detect treatment failure and switch to second‐line ART has also increased. We assessed CD4 cell counts (as a marker of treatment failure), determined the rate of switching to second‐line treatment and evaluated mortality related to treatment failure among HIV‐infected patients in Guinea‐Bissau. Methods: In this retrospective cohort study, adult patients infected with HIV‐1 receiving ≥6 months of ART at an HIV clinic in Bissau were included from June 2005 to July 2014 and followed until January 2015. Treatment failure was defined as 1) a fall in CD4 count to baseline (or below) or 2) CD4 levels persistently below 100 cells/µL after ≥6 months of ART. Cox hazard models, with time since six months of ART as the time‐varying coefficient, were used to estimate the hazard ratio for death and loss to follow‐up. Results: We assessed 1,591 HIV‐1‐infected patients for immunological treatment failure. Treatment failure could not be determined in 594 patients (37.3%) because of missing CD4 cell counts. Among the remaining 997 patients, 393 (39.4%) experienced failure. Only 39 patients (9.9%) with failure were switched from first‐ to second‐line ART. The overall switching rate was 3.1 per 100 person‐years. Mortality rate was higher in patients with than without treatment failure, with adjusted hazard rate ratios (HRRs) 10.0 (95% CI: 0.9–107.8), 7.6 (95% CI: 1.6–35.5) and 3.1 (95% CI: 1.5–6.3) in the first, second and following years, respectively. During the first year of follow‐up, patients experiencing treatment failure had a higher risk of being lost to follow‐up than patients not experiencing treatment failure (adjusted HRR 4.4; 95% CI: 1.7–11.8). Conclusions: We found a high rate of treatment failure, an alarmingly high number of patients for whom treatment failure could not be assessed, and a low rate of switching to a second‐line therapy. These factors could lead to an increased risk of resistance development and excess mortality., Introduction With the rapid scale‐up of antiretroviral treatment (ART) availability in sub‐Saharan Africa, the need for appropriate treatment monitoring has also increased [1]. As more people receive ART, more will [...]

Purpose: To estimate the life expectancy (LE) of HIV-infected patients in the West African country Guinea-Bissau and compare it with the background population. Methods: Using data from the largest HIV outpatient clinic at the Hospital Nacional Simão Mendes in the capital Bissau, a retrospective observational cohort study was performed. The study included patients attending the clinic between June 2005 and January 2018. A total of 8958 HIV-infected patients were included. In the analysis of the background population, a total of 109,191 people were included. LE incorporating loss to follow-up (LTFU) was estimated via Kaplan–Meier estimators using observational data on adult HIV-infected patients and background population. Results: The LE of 20-year-old HIV-infected patients was 9.8 years (95% CI 8.3–11.5), corresponding to 22.3% (95% CI 18.5–26.7%) of the LE of the background population. (LE for 20-year-olds in the background population was 44.0 years [95% CI 43.0–44.9].) Patients diagnosed with CD4 cell counts below 200 cells/µL had a LE of 5.7 years (95% CI 3.6–8.2). No increase in LE with later calendar period of diagnosis was observed. Conclusions: LE was shown to be markedly lower among HIV-infected patients compared with the background population. While other settings have shown marked improvements in prognosis of HIV-infected patients in recent years, no improvement in Bissau was observed over time (9.8 years (95% CI 7.6–12.2) and 9.9 years (95% CI 7.6–12.1) for the periods 2005–2010 and 2014–2016, respectively). [ABSTRACT FROM AUTHOR]

Abstract Background Brain abscess is a potentially fatal disease. This study assesses clinical aspects of brain abscess in a large hospital cohort. Methods Retrospective review of adult patients with pyogenic brain abscess at Rigshospitalet University Hospital, Denmark between 1994 and 2009. Prognostic factors associated with Glasgow Outcome Score (GOS) (death, severe disability or vegetative state) were assessed by logistic regression. Results 102 patients were included. On admission, only 20% of patients had a triad of fever, headache and nausea, 39% had no fever, 26% had normal CRP and 49% had no leucocytosis. Median delay from symptom onset to antibiotic treatment was 7 days (range 0–97 days). Source of infection was contiguous in 36%, haematogenous in 28%, surgical or traumatic in 9% and unknown in 27% of cases. Abscess location did not accurately predict the portal of entry. 67% were treated by burr hole aspiration, 20% by craniotomy and 13% by antibiotics alone. Median duration of antibiotic treatment was 62 days. No cases of recurrent abscess were observed. At discharge 23% had GOS ≤3. The 1-, 3- and 12-month mortality was 11%, 17% and 19%. Adverse outcome was associated with a low GCS at admission, presence of comorbidities and intraventricular rupture of abscess. Conclusions The clinical signs of brain abscess are unspecific, many patients presented without clear signs of infection and diagnosis and treatment were often delayed. Decreased GCS, presence of comorbidities and intraventricular rupture of brain abscess were associated with poor outcome. Brain abscess remains associated with considerable morbidity and mortality.

Abstract Background Our objective was to evaluate and compare the effect of abacavir on levels of biomarkers associated with cardiovascular risk. Methods In an open-label randomized trial, HIV-infected patients were randomized 1:1 to switch from zidovudine/lamivudine to abacavir/lamivudine or tenofovir/emtricitabine. In the present analysis, we measured levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), E-selectin, and myeloperoxidase (MPO) at baseline and 4, 12, and 48 weeks after randomization. D-dimer and fasting lipids were measured at baseline and weeks 12 and 48. Levels of biomarkers at all time points and changes from baseline were compared across study arms using Wilcoxon rank sum test. Results Of 40 included patients, 35 completed 48 weeks of randomized therapy and follow up. Levels of E-selectin (P = 0.004) and sVCAM-1 (P = 0.041) increased transiently from baseline to week 4 in the abacavir arm compared with the tenofovir arm, but no long-term increases were detected. We found no significant differences between study arms in the levels or changes in the levels of sICAM-1, MPO, d-dimer, IL-6, or hs-CRP. Levels of total cholesterol and high density lipoprotein (HDL) increased in the abacavir arm relative to the tenofovir arm, but no difference was found in total cholesterol/HDL ratio. Conclusion In patients randomized to abacavir-based HIV-treatment transient increases were seen in the plasma levels of E-selectin and sVCAM-1 compared with treatment with tenofovir, but no difference between study arms was found in other biomarkers associated with endothelial dysfunction, inflammation, or coagulation. The clinical significance of these findings is uncertain. Trial Regestration Clinicaltrials.gov identifier: NCT00647244.

Abstract Background The effect of peginterferon and ribavirin treatment on chronic hepatitis C virus (HCV) infection has been established in several controlled clinical studies. However, the effectiveness of treatment and predictors of treatment success in routine clinical practice remains to be established. Our aim was to estimate the effectiveness of peginterferon and ribavirin treatment in unselected HCV patients handled in routine clinical practice. The endpoint was sustained virological response (SVR), determined by the absence of HCV RNA 24 weeks after the end of treatment. Methods We determined the proportion of SVR in a nationwide, population-based cohort of 432 patients with chronic HCV infection who were starting treatment, and analyzed the impact of known covariates on SVR by using a logistic regression analysis. Results The majority of treated patients had genotype 1 (133 patients) and genotype 2/3 (285 patients) infections, with 44% and 72%, respectively, obtaining SVR. Other than genotype, the predictors of SVR were age ≤ 45 years at the start of treatment, completion of unmodified treatment, the absence of cirrhosis and non-European origin. Conclusions The effectiveness of peginterferon and ribavirin treatment for chronic hepatitis C in a routine clinical practice is comparable to that observed in controlled clinical trials, with a higher SVR rate in genotype 2 and 3 patients compared to genotype 1 patients. Our data further indicate that age at start of treatment is a strong predictor of SVR irrespective of HCV genotype, with patients 45 years or younger having a higher SVR rate.

Direct‐acting antivirals (DAAs) have proven highly effective against chronic hepatitis C virus (HCV) infection. However, some patients experience treatment failure, associated with resistance‐associated substitutions (RASs). Our aim was to investigate the complete viral coding sequence in hepatitis C patients treated with DAAs to identify RASs and the effects of treatment on the viral population. We selected 22 HCV patients with sustained virologic response (SVR) to match 21 treatment‐failure patients in relation to HCV genotype, DAA regimen, liver cirrhosis and previous treatment experience. Viral‐titre data were compared between the two patient groups, and HCV full‐length open reading frame deep‐sequencing was performed. The proportion of HCV NS5A‐RASs at baseline was higher in treatment‐failure (82%) than matched SVR patients (25%) (p =.0063). Also, treatment failure was associated with slower declines in viraemia titres. Viral population diversity did not differ at baseline between SVR and treatment‐failure patients, but failure was associated with decreased diversity probably caused by selection for RAS. The NS5B‐substitution 150V was associated with sofosbuvir treatment failure in genotype 3a. Further, mutations identified in NS2, NS3‐helicase and NS5A‐domain‐III were associated with DAA treatment failure in genotype 1a patients. Six retreated HCV patients (35%) experienced 2nd treatment failure; RASs were present in 67% compared to 11% with SVR. In conclusion, baseline RASs to NS5A inhibitors, but not virus population diversity, and lower viral titre decline predicted HCV treatment failure. Mutations outside of the DAA targets can be associated with DAA treatment failure. Successful DAA retreatment in patients with treatment failure was hampered by previously selected RASs. [ABSTRACT FROM AUTHOR]