Human monkeypox virus infection in women and non-binary individuals during the 2022 outbreaks: a global case series.

BACKGROUND: Between May and November, 2022, global outbreaks of human monkeypox virus infection have been reported in more than 78 000 people worldwide, predominantly in men who have sex with men. We describe the epidemiological and clinical characteristics of monkeypox virus infection in cisgender (cis) and transgender (trans) women and non-binary individuals assigned female sex at birth to improve identification and understanding of risk factors. METHODS: International collaborators in geographical locations with high numbers of diagnoses of monkeypox virus infection were approached and invited to contribute data on women and non-binary individuals with confirmed monkeypox virus infection. Contributing centres completed deidentified structured case-report spreadsheets, adapted and developed by participating clinicians, to include variables of interest relevant to women and non-binary individuals assigned female at birth. We describe the epidemiology and clinical course observed in the reported infections. FINDINGS: Collaborators reported data for a total of 136 individuals with monkeypox virus infection who presented between May 11 and Oct 4, 2022, across 15 countries. Overall median age was 34 years (IQR 28-40; range 19-84). The cohort comprised 62 trans women, 69 cis women, and five non-binary individuals (who were, because of small numbers, grouped with cis women to form a category of people assigned female at birth for the purpose of comparison). 121 (89%) of 136 individuals reported sex with men. 37 (27%) of all individuals were living with HIV, with a higher proportion among trans women (31 [50%] of 62) than among cis women and non-binary individuals (six [8%] of 74). Sexual transmission was suspected in 55 (89%) trans women (with the remainder having an unknown route of transmission) and 45 (61%) cis women and non-binary individuals; non-sexual routes of transmission (including household and occupational exposures) were reported only in cis women and non-binary individuals. 25 (34%) of 74 cis women and non-binary individuals submitted to the case series were initially misdiagnosed. Overall, among individuals with available data, rash was described in 124 (93%) of 134 individuals and described as anogenital in 95 (74%) of 129 and as vesiculopustular in 105 (87%) of 121. Median number of lesions was ten (IQR 5-24; range 1-200). Mucosal lesions involving the vagina, anus, or oropharynx or eye occurred in 65 (55%) of 119 individuals with available data. Vaginal and anal sex were associated with lesions at those sites. Monkeypox virus DNA was detected by PCR from vaginal swab samples in all 14 samples tested. 17 (13%) individuals were hospitalised, predominantly for bacterial superinfection of lesions and pain management. 33 (24%) individuals were treated with tecovirimat and six (4%) received post-exposure vaccinations. No deaths were reported. INTERPRETATION: The clinical features of monkeypox in women and non-binary individuals were similar to those described in men, including the presence of anal and genital lesions with prominent mucosal involvement. Anatomically, anogenital lesions were reflective of sexual practices: vulvovaginal lesions predominated in cis women and non-binary individuals and anorectal features predominated in trans women. The prevalence of HIV co-infection in the cohort was high. FUNDING: None.

Potential drug-drug interactions between antiretroviral drugs and comedications, including dietary supplements, among people living with HIV: A clinical survey.

OBJECTIVE: Age-related comorbidities, polypharmacy and thereby the risk of potential drug-drug interactions (PDDIs) among people living with HIV (PLWH) have increased over the years. We estimated the prevalence of comedications, including dietary supplements, and evaluated PDDIs among PLWH receiving antiretroviral therapy (ART) in Denmark in an outpatient setting. METHODS: Information on prescription medication, over-the-counter medication and dietary supplements was obtained from adult PLWH receiving ART attending two outpatient clinics in Denmark. The PDDIs were identified using the University of Liverpool's drug interaction database. Associations between PDDIs and relevant variables were compared using logistic regression models. RESULTS: A total of 337 PLWH receiving ART with a median age of 53 years (interquartile range: 45-61) were included; 77% were male and 96% had a HIV-RNA viral load < 50 copies/mL. Twenty-six per cent of participants received five or more comedications and 56% consumed dietary supplements. Co-administration of drugs requiring dose adjustment or monitoring was identified in the medication lists of 52% of participants, and 4.5% were on drugs that should not be co-administered. Male sex [odds ratio (OR) = 1.9, 95% confidence interval (CI): 1.0-3.4], being on a protease inhibitor (OR = 4.3, 95% CI: 1.9-9.7), receiving five or more comedications (OR = 3.3, 95% CI: 1.5-7.2), taking over-the-counter medications (OR = 1.9, 95% CI: 1.1-3.3) and dietary supplements (OR = 2.0, 95% CI: 1.2-3.3) were independent predictors of PDDIs. CONCLUSION: Potential drug-drug interactions were common among our study population Our study confirms that polypharmacy and being on a protease inhibitor-based regimen increase the risk of PDDIs considerably and highlights the importance of questioning PLWH about dietary supplement intake.

Length of stay in Denmark before HIV diagnosis and linkage to care: a population-based study of migrants living with HIV, Denmark, 1995 to 2020.

BackgroundMigrants face an increased risk of HIV infection and late presentation for HIV care.AimTo examine delays in HIV diagnosis, linkage to care (LTC), and risk of late presentation for migrants living with HIV in Denmark.MethodsWe conducted a population-based, nationwide study of adult migrants (n = 2,166) presenting for HIV care between 1 January 1995 and 31 December 2020 in Denmark. Time from immigration to HIV diagnosis and from diagnosis to LTC, and late presentation were assessed, stratified by migrants' geographical regions of origin, using descriptive statistics.ResultsThe demographics of the migrant population changed over time. Overall, migrants diagnosed with HIV after immigration to Denmark resided a median of 3.7 (IQR: 0.8-10.2) years in Denmark before diagnosis. Median time from HIV diagnosis to LTC was 6 (IQR: 0-24) days. Migrants diagnosed with HIV infection before immigration had a median of 38 (IQR: 0-105) days from arrival in Denmark to LTC. The corresponding median times for 2015-20 alone were 4.1 (IQR: 0.9-13.1) years, 0 (IQR: 0-8) days, and 62 (IQR: 25-152) days, respectively. The overall proportion of late presentation among migrants diagnosed with HIV after immigration was 60%, and highest among migrants from sub-Saharan Africa and East and South Asia.ConclusionHIV diagnosis is still substantially delayed in Danish migrants, while LTC is timely. The proportions with late presentation are high. These results call for targeted interventions to reduce the number of migrants with undiagnosed HIV infections and of late presenters.

Complete manuscript Title: Changes in RANKL during the first two years after cART initiation in HIV-infected cART naïve adults.

BACKGROUND: By assessing the changes in concentration of soluble receptor activator of nuclear factor κ B ligand (RANKL) and osteoprotegrin (OPG) after initiation of combination antiretroviral therapy (cART) in treatment-naïve HIV-infected patients we aimed to evaluate whether the initial accelerated bone loss could be mediated by increased soluble RANKL (sRANKL) levels associated with CD4+ T cell recovery. METHODS: We used multiplex immunoassays to determine sRANKL and OPG concentrations in plasma from 48 HIV patients at baseline and 12, 24, 48 and 96 weeks after cART initiation. RESULTS: Soluble RANKL changed significantly over time (overall p = 0.02) with 25% decrease (95% CI: -42 to -5) at week 24 compared to baseline and stabilized at a lower level thereafter. We found no correlation between CD4+ T cell count increment and changes in sRANKL or between percentage change in BMD and changes in sRANKL. CONCLUSION: In this study there was no indication that the accelerated bone loss after cART initiation was mediated by early changes in sRANKL due to CD4+ T cell recovery. Future studies should focus on the initial weeks after initiation of cART. TRIAL REGISTRATION: Clinical-Trial.gov . id NCT00135460 , August 25, 2005. The study was approved by the Danish Data Protection Agency, Danish Medicines Agency and Regional Ethics Committee.

Fracture risk in hepatitis C virus infected persons: results from the DANVIR cohort study.

BACKGROUND & AIMS: The association between Hepatitis C virus (HCV)-infection and fracture risk is not well characterized. We compared fracture risk between HCV-seropositive (HCV-exposed) patients and the general population and between patients with cleared and chronic HCV-infection. METHODS: Outcome measures were time to first fracture at any site, time to first low-energy and first non-low-energy (other) fracture in 12,013 HCV-exposed patients from the DANVIR cohort compared with a general population control cohort (n=60,065) matched by sex and age. Within DANVIR, 4500 patients with chronic HCV-infection and 2656 patients with cleared HCV-infection were studied. RESULTS: Compared with population controls, HCV-exposed patients had increased overall risk of fracture [adjusted incidence rate ratio (aIRR) 2.15, 95% Confidence Interval (CI) 2.03-2.28], increased risk of low-energy fracture (aIRR 2.13, 95% CI: 1.93-2.35) and of other fracture (aIRR 2.18, 95% CI: 2.02-2.34). Compared with cleared HCV-infection, chronic HCV-infection was not associated with increased risk of fracture at any site (aIRR 1.08, 95% CI: 0.97-1.20), or other fracture (aIRR 1.04, 95% CI: 0.91-1.19). The aIRR for low-energy fracture was 1.20 (95% CI: 0.99-1.44). CONCLUSIONS: HCV-exposed patients had increased risk of all fracture types. In contrast, overall risk of fracture did not differ between patients with chronic vs. cleared HCV-infection, although chronic HCV-infection might be associated with a small excess risk of low-energy fractures. Our study suggests that fracture risk in HCV-infected patients is multi-factorial and mainly determined by lifestyle-related factors associated with HCV-exposure.

Two anthrax cases with soft tissue infection, severe oedema and sepsis in Danish heroin users.

BACKGROUND: Anthrax had become extremely rare in Europe, but in 2010 an outbreak of anthrax among heroin users in Scotland increased awareness of contaminated heroin as a source of anthrax. We present the first two Danish cases of injectional anthrax and discuss the clinical presentations, which included both typical and more unusual manifestations. CASE PRESENTATIONS: The first patient, a 55-year old man with HIV and hepatitis C virus co-infection, presented with severe pain in the right thigh and lower abdomen after injecting heroin into the right groin. Computed tomography and ultrasonographic examination of the abdomen and right thigh showed oedematous thickened peritoneum, distended oedematous mesentery and subcutaneous oedema of the right thigh. At admission the patient was afebrile but within 24 hours he progressed to severe septic shock and abdominal compartment syndrome. Cultures of blood and intraperitoneal fluid grew Bacillus anthracis. The patient was treated with meropenem, clindamycin, ciprofloxacin and metronidazole. Despite maximum supportive care including mechanical ventilation, vasopressor treatment and continuous veno-venous hemodiafiltration the patient died on day four.The second patient, a 39-year old man with chronic hepatitis C virus infection, presented with fever and a swollen right arm after injecting heroin into his right arm. The arm was swollen from the axilla to the wrist with tense and discoloured skin. He was initially septic with low blood pressure but responded to crystalloids. During the first week, swelling progressed and the patient developed massive generalised oedema with a weight gain of 40 kg. When blood cultures grew Bacillus anthracis antibiotic treatment was changed to meropenem, moxifloxacin and metronidazole, and on day 7 hydroxycloroquin was added. The patient responded to treatment and was discharged after 29 days. CONCLUSIONS: These two heroin-associated anthrax cases from Denmark corroborate that heroin contaminated with anthrax spores may be a continuous source of injectional anthrax across Europe. Clinicians and clinical microbiologists need to stay vigilant and suspect anthrax in patients with a history of heroin use who present with soft tissue or generalised infection. Marked swelling of affected soft tissue or unusual intra-abdominal oedema should strengthen clinical suspicion.

Patient-reported outcomes in clinical HIV care: protocol for a single-centre, multistage, mixed-methods study in Denmark.

INTRODUCTION: People with HIV-1 (PWH) have worse health-related quality of life (HRQoL) compared with the general population. Using patient-reported outcomes (PROs) may help reorient the focus of HIV care towards improving HRQoL. This study aims to develop, implement and evaluate the use of PROs in HIV care. METHODS AND ANALYSIS: This is a Danish single-centre, multistage mixed-methods study consisting of four substudies (studies I-IV). Study I is a qualitative focus group interview study aiming to identify relevant PRO domains, and barriers and benefits to PRO use. Participants are 5-10 PWH and 5-10 HIV healthcare providers (HCPs). Data are thematically analysed. Results will guide the design of a PRO measure (PROM). Study II is a quantitative study aiming to assess PWH's willingness and ability to engage with PRO. All PWH are consecutively invited to complete the PROMs before their next consultations. Demographic data are collected at enrolment. Differences between PWH who do/do not complete the PROMs are assessed. Study III is a quantitative before-and-after study aiming to assess the impact of PRO use on HCP awareness. Participants are all who complete the PROMs in Study II. In contrast to study II, HCPs are notified of the PROM results. The number of problems documented by the HCP in patients' medical records during studies II and III are compared using χ2 tests. Multiple regression models are used to identify factors associated with HCP awareness. Study IV is a qualitative study aiming to explore PWH and HCP experiences of using PROs. Participants are 15-20 PWH and 10-15 HCP. Data are collected from participant observation of PRO consultations and individual interviews. Data are analysed thematically. ETHICS AND DISSEMINATION: This study is approved by the Danish Data Protection Agency. Participants will provide written consent prior to participation. Results will be published in peer-reviewed journals.

Chronic appendicitis: two case reports.

BACKGROUND: Chronic appendicitis is a condition unfamiliar to many physicians and is often referred to as a controversial diagnosis. This can give rise to diagnostic delay. CASE PRESENTATION: We present two cases of chronic appendicitis: a Caucasian female aged 21 years and a Caucasian male aged 34 years. The patients had different clinical presentations, which led the initial investigations in very different directions-tropical infectious disease and possible malignancy, respectively. In both cases, radiological imaging was the key investigation leading to the final surprising diagnosis. CONCLUSION: With these two case stories, we wish to draw attention to chronic appendicitis as a possible differential diagnosis in younger patients with chronic or recurrent abdominal pain, particularly if the pain is located in the lower abdomen and is accompanied by fever.

Outcome of SARS-CoV-2 infection among patients with common variable immunodeficiency and a matched control group: A Danish nationwide cohort study.

The risk of severe adult respiratory coronavirus-2 (SARS-CoV-2) infection and the course of the infection among individuals with common variable immunodeficiency (CVID) relative to the general population have been a matter of debate. We conducted a Danish nationwide study comparing the timing of SARS-CoV-2 vaccination, the risk of first confirmed SARS-CoV-2 infection, re-infection, and the outcome of infection among individuals with CVID relative to an age- and gender matched control group. Cox regression was used to calculate incidence rate ratios. The CVID patients received SARS-CoV-2 vaccinations earlier than those included in the population control group. Even so, the risks of both first infection and re-infection were increased among the individuals with CVID. The CVID group also had increased risk for hospital contacts due to SARS-CoV-2 infection relative to the general population. However, reassuringly, the risk of mechanical ventilation and death did not differ between the groups, but the numbers were low in both groups, making the estimates uncertain. Though this is the largest study to investigate the risk of SARS-CoV-2 infections and outcomes hereof among individuals with CVID relative to the general population, we cannot rule out minor differences in severity, which might only be detectable with an even larger sample size.

[Pneumocystis pneumonia and HIV infection in two patients suspected with COVID-19].

Pneumocystis pneumonia (PCP) in undiagnosed HIV-positive individuals and COVID-19 patients share many of the same clinical features. This case report describes two patients admitted to hospital during the COVID-19 pandemic. Both suffered from dyspnoea, dry cough and fever, showed signs of underlying illness and had severe hypoxia, elevated lactate dehydrogenase levels and lymfocytopenia. COVID-19 was suspected despite several negative tests. Both patients tested positive for PCP and HIV. In cases with unexplained interstitial pneumonia, PCP and underlying immunodeficiency should be suspected, and an HIV-test should be performed.

Low morbidity in Danish patients with common variable immunodeficiency disorder infected with severe acute respiratory syndrome coronavirus 2.

BACKGROUND: Manifestations and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not well documented in patients with common variable immunodeficiency disorder (CVID). METHODS: A Danish nationwide retrospective clinician-reported survey. RESULTS: Eleven patients with CVID and SARS-CoV-2 infection were identified. The median age was 50 years (range 22-72). All were on immunoglobulin replacement therapy. Eight patients had other pre-existing co-morbidities. Three patients were asymptomatic during the SARS-CoV-2 infection while seven developed mild coronavirus disease 2019 (COVID-19). One patient had more severe disease with hypoxia and required oxygen therapy. This patient had multiple co-morbidities including well known risk factors for severe COVID-19. All patients recovered. CONCLUSIONS: The results suggest that CVID may not be a risk factor for severe COVID-19. However, further monitoring of this immunodeficient population is needed to confirm our observation.

Unmeasured confounding caused slightly better response to HAART within than outside a randomized controlled trial.

OBJECTIVE: To compare the outcome of highly active antiretroviral therapy (HAART) in HIV-infected patients initiating equivalent regimens within and outside a randomized controlled trial (RCT). STUDY DESIGN AND SETTING: The Danish Protease Inhibitor Study (DAPIS) was a national multicenter RCT comparing initial treatment with indinavir, ritonavir, or saquinavir/ritonavir during 96 weeks. From the Danish HIV Cohort Study we identified all patients initiating one of these protease-inhibitor-based HAART regimens: 425 patients within DAPIS and 677 outside the trial. We compared viral load, CD4 count response, and mortality. RESULTS: At weeks 96 and 240, trial participants were more likely than nonparticipants to have undetectable viral load (adjusted odds ratio [adOR] 1.28 [95% CI=0.94-1.74] and 1.70 [95% CI=1.16-2.50]) and a CD4 increase > or =100 cells/microl (adOR 1.37 [95% CI=1.03-1.82] and 1.53 [95% CI=1.04-2.25]). For antiretroviral-experienced, but not for antiretroviral-naïve patients, trial participants had a lower risk of death (mortality rate ratio [MRR]=0.46 [95% CI=0.27-0.77]) than nonparticipants. This effect was moderated in adjusted analyses (MRR=0.60 [0.33-1.07]). CONCLUSIONS: Compared to nontrial patients, trial participants had better response to HAART. The differences were small defying the notion that results obtained in RCTs are unachievable in routine clinical practice.

Survival of persons with and without HIV infection in Denmark, 1995-2005.

BACKGROUND: The expected survival of HIV-infected patients is of major public health interest. OBJECTIVE: To estimate survival time and age-specific mortality rates of an HIV-infected population compared with that of the general population. DESIGN: Population-based cohort study. SETTING: All HIV-infected persons receiving care in Denmark from 1995 to 2005. PATIENTS: Each member of the nationwide Danish HIV Cohort Study was matched with as many as 99 persons from the general population according to sex, date of birth, and municipality of residence. MEASUREMENTS: The authors computed Kaplan-Meier life tables with age as the time scale to estimate survival from age 25 years. Patients with HIV infection and corresponding persons from the general population were observed from the date of the patient's HIV diagnosis until death, emigration, or 1 May 2005. RESULTS: 3990 HIV-infected patients and 379,872 persons from the general population were included in the study, yielding 22,744 (median, 5.8 y/person) and 2,689,287 (median, 8.4 years/person) person-years of observation. Three percent of participants were lost to follow-up. From age 25 years, the median survival was 19.9 years (95% CI, 18.5 to 21.3) among patients with HIV infection and 51.1 years (CI, 50.9 to 51.5) among the general population. For HIV-infected patients, survival increased to 32.5 years (CI, 29.4 to 34.7) during the 2000 to 2005 period. In the subgroup that excluded persons with known hepatitis C coinfection (16%), median survival was 38.9 years (CI, 35.4 to 40.1) during this same period. The relative mortality rates for patients with HIV infection compared with those for the general population decreased with increasing age, whereas the excess mortality rate increased with increasing age. LIMITATIONS: The observed mortality rates are assumed to apply beyond the current maximum observation time of 10 years. CONCLUSIONS: The estimated median survival is more than 35 years for a young person diagnosed with HIV infection in the late highly active antiretroviral therapy era. However, an ongoing effort is still needed to further reduce mortality rates for these persons compared with the general population.

[Periodic fever syndromes].

Periodic fever syndromes (PFS) are characterised by recurrent fever and excessive systemic inflammation. These rare and hereditary syndromes include familial Mediterranean fever, tumour necrosis factor receptor-1 associated periodic syndrome, mevalonate kinase deficiency and cryopyrin-associated periodic syndrome. Each PFS has distinct clinical and genetic features. Availability of improved genetic methods has improved the understanding of the syndromes and diagnostic testing. The main complication is systemic amyloidosis. Targeted biological therapy such as interleukin-1 inhibitors is emerging as an effective treatment.

Current hemoglobin levels are more predictive of disease progression than hemoglobin measured at baseline in patients receiving antiretroviral treatment for HIV type 1 infection.

The role of hemoglobin levels as an independent prognostic marker of progression to AIDS and/or death in HIV-infected patients starting combination antiretroviral therapy (cART) was investigated. A total of 2,579 patients from the EuroSIDA cohort with hemoglobin, CD4 cell count, and HIV RNA viral load measured 6 months prior to starting cART was included in the analyses. Anemia was defined as mild (

[The significance of HIV to bone mineral density].

The life expectancy in well-treated HIV-infected persons approaches that of the general population, but HIV-infected persons have a greater incidence of fractures and osteoporosis. A decrease in bone mineral density is observed primarily during the first 1-2 years of antiretroviral therapy. Dual X-ray absorptiometry scan should be considered in HIV-infected men ≥ 50 years and postmenopausal women. In case of osteoporosis, bisphosphonate treatment should follow guidelines for the general population. Future research should focus on pathogenesis and prevention of bone density loss in HIV.

Adipose tissue expression of IL-18 and HIV-associated lipodystrophy.

IL-18 is an inducer of apoptosis/tissue injury. IL-18 messenger RNA expression was examined in adipose tissue (AT) obtained from HIV patients with lipodystrophy, without lipodystrophy and healthy controls. IL-18 mRNA was expressed in AT at increased levels in lipodystrophy-positive compared with lipodystrophy-negative patients and healthy controls. Higher levels of IL-18 mRNA were found in femoral-gluteal AT compared with abdominal AT, and correlated with limb fat loss. These findings suggest that IL-18 is linked to HIV-associated lipodystrophy.

[The HIV population is aging]. / Antallet af ældre patienter med hiv er støt stigende

The HIV population is aging due to increased life expectancy among HIV patients on antiretroviral therapy. 37% of Danish HIV patients are now older than 50 years. Older age has implications for all stages of HIV care. Older patients are at higher risk of delayed HIV diagnosis and thereby less favourable prognosis. Factors related directly to HIV infection, lifestyle-related factors and co-infections contribute to increased prevalence of co-morbidity in older HIV patients, and medical treatments of co-morbidity together with three or more antiviral drugs increase the risk of polypharmacy.

Inpatient admissions and outpatient visits in persons with and without HIV infection in Denmark, 1995-2007.

OBJECTIVE: HAART has changed morbidity and mortality in the HIV-infected population dramatically. We aimed to estimate the use of healthcare facilities in HIV-infected patients after the introduction of HAART. DESIGN: This is a prospective nationwide cohort study. METHODS: We identified all Danish HIV patients and a cohort of population controls matched on sex and date of birth. The study period was 1995-2007. We calculated inpatient admission rates and outpatient visit rates stratified by medical speciality and International Classification of Diseases-10 diagnose categories. Relative risks were computed. RESULTS: Four thousand, seven hundred and sixty HIV-infected patients and 23 800 population controls were identified. Overall inpatient admission rates [95% confidence interval (CI)] for HIV-infected patients decreased from 90 (88-93) to 57 (56-58)/100 person-years in the study period. The risk ratio (95% CI) fell from 6.2 (6.0-6.5) to 3.1 (3.1-3.2) predominantly due to reduced inpatient admission rates to departments of infectious diseases. The overall outpatient visit rates (95% CI) for the HIV-infected patients increased from 744 (737-751) to 877 (872-882)/100 person-years, mainly due to visits at departments other than infectious diseases. A marked increase in outpatient visit rates (95% CI) in the background population decreased the risk ratio from 16.5 (16.2-16.8) to 7.1 (7.0-7.2). We observed a decreased relative risk of inpatient admissions and outpatient visits due to cancers and a small increase in relative risk due to cardiovascular disease. CONCLUSION: After the introduction of HAART, the inpatient treatment of HIV-infected patients has decreased, especially at departments of infectious disease. In contrast, this population's use of outpatient facilities has increased in noninfectious disease specialities.