Evolving AIDS- and non-AIDS Mortality and Predictors in the PISCIS Cohort of People Living With HIV in Catalonia and the Balearic Islands (Spain), 1998-2020.

Background: Effective antiretroviral therapy (ART) has substantially reduced acquired immunodeficiency syndrome (AIDS)-related deaths, shifting the focus to non-AIDS conditions in people living with human immunodeficiency virus (HIV) (PLWH). We examined mortality trends and predictors of AIDS- and non-AIDS mortality in the Population HIV Cohort from Catalonia and Balearic Islands (PISCIS) cohort of PLWH from 1998 to 2020. Methods: We used a modified Coding Causes of Death in HIV protocol, which has been widely adopted by various HIV cohorts to classify mortality causes. We applied standardized mortality rates (SMR) to compare with the general population and used competing risks models to determine AIDS-related and non-AIDS-related mortality predictors. Results: Among 30 394 PLWH (81.5% male, median age at death 47.3), crude mortality was 14.2 per 1000 person-years. All-cause standardized mortality rates dropped from 9.6 (95% confidence interval [CI], 8.45-10.90) in 1998 through 2003 to 3.33 (95% CI, 3.14-3.53) in 2015 through 2020, P for trend = .0001. Major causes were AIDS, non-AIDS cancers, cardiovascular disease, AIDS-defining cancers, viral hepatitis, and nonhepatitis liver disease. Predictors for AIDS-related mortality included being aged ≥40 years, not being a man who have sex with men, history of AIDS-defining illnesses, CD4 < 200 cells/µL, ≥2 comorbidities, and nonreceipt of ART. Non-AIDS mortality increased with age, injection drug use, heterosexual men, socioeconomic deprivation, CD4 200 to 349 cells/µL, nonreceipt of ART, and comorbidities, but migrants had lower risk (adjusted hazard risk, 0.69 [95% CI, .57-.83]). Conclusions: Mortality rates among PLWH have significantly decreased over the past 2 decades, with a notable shift toward non-AIDS-related causes. Continuous monitoring and effective management of these non-AIDS conditions are essential to enhance overall health outcomes.

Major cardiovascular events after COVID-19 in people with HIV.

OBJECTIVES: To assess the effect of COVID-19 on the postacute risk of cardiovascular events (CVEs) among people with HIV (PWH). METHODS: Population-based matched cohort, including all PWH ≥16 years in the Catalan PISCIS HIV cohort. We estimated the incidence rate of the first CVE after COVID-19, analysed it a composite outcome (2020-2022). We adjusted for baseline differences using inverse probability weighting and used competing risk analysis. RESULTS: We included 4199 PWH with and 14 004 PWH without COVID-19. The median follow-up was 243 days (interquartile range [IQR]: 93-455), 82% (14 941/18 203) were men, with a median age of 47 years. Overall, 211 PWH with COVID-19 and 621 without developed CVE, with an incidence rate of 70.2 and 56.8/1000 person-years, respectively. During COVID-19 infection, 7.6% (320/4199) required hospitalization and 0.6% (25/4199) intensive care unit admission, 97% (4079/4199) had CD4+T-cell ≥200 cells/µL, 90% (3791/4199) had HIV-RNA<50 copies/mL and 11.8% (496/4199) had previous CVE at baseline. The cumulative CVE incidence was higher among PWH after COVID-19 compared with PWH without COVID-19 during the first year (log-rank p=0.011). The multivariable analysis identified significantly increased CVE risk with age, heterosexual men, previous cardiovascular disease (CVD), and chronic kidney or liver disease. COVID-19 was associated with increased subsequent risk of CVE (adjusted hazard ratio 1.30 [95% CI, 1.09-1.55]), also when only including individuals without previous CVD (1.60 [95% CI, 1.11-2.29]) or nonhospitalized patients (1.34 [95% CI, 1.11-1.62]). DISCUSSION: COVID-19 was associated with a 30% increased risk of major CVE in PWH during the subsequent year, suggesting that COVID-19 should be considered an additional CVD risk in PWH in the short term.

Mpox: Clinical Outcomes and Impact of Vaccination in People with and without HIV: A Population-Wide Study.

We investigated differences in mpox clinical outcomes in people with HIV (PWH) and without HIV (PWoH) and the impact of vaccination in Catalonia, Spain. We used surveillance data and the PISCIS HIV cohort. We included all confirmed mpox cases (May-December 2022). Of 2122 mpox cases, the majority had mild disease, 56% were Spanish, and 24% were from Latin America. A total of 40% were PWH, with a median CD4+T-cell of 715 cells/µL; 83% had HIV-RNA < 50 copies/mL; and 1.8% CD4+T-cell < 200 cells/µL. PWH had no increased risk for complications, except those with CD4+T-cell < 200 cells/µL. PWH with CD4+T-cell < 200 cells/µL were more likely to be from Latin America, had more generalized exanthema, and required hospitalization more frequently (p = 0.001). Diagnosis of other sexually transmitted infections (STIs) was common, both at mpox diagnosis (17%) and two years before (43%). Dose-sparing smallpox intradermal vaccination was accompanied by a sharp decrease in mpox incidence in both populations (p < 0.0001). In conclusion, unless immunosuppressed, PWH were not at increased risk of severe disease or hospitalization. Mpox is a marker of high-risk sexual behavior and was associated with high HIV and STI rates, supporting the need for screening in all mpox cases. Ethnicity disparities demonstrate the need for interventions to ensure equitable healthcare access. Dose-sparing smallpox vaccination retained effectiveness.

Evaluating Drug Prescription Patterns in Undiagnosed Common Variable Immunodeficiency Patients.

OBJECTIVE: To compare the consumption of antibiotics (AB), systemic steroids, and inhaled bronchodilators/glucocorticoids in the 3 years preceding the diagnosis of common variable immunodeficiency (CVID) among CVID patients and matched controls and to estimate whether the level of consumption was associated with the risk of a subsequent CVID diagnosis. METHODS: We conducted a nested case-control study, identifying all individuals (n=130 cases) diagnosed with CVID in Denmark (1994-2014) and 45 age- and sex-matched population controls per case (n=5850 controls) from national registers. Drug consumption was estimated as defined daily doses per person-year. We used conditional logistic regression to compute odds ratios and 95% confidence intervals. RESULTS: In the 3 years preceding a CVID diagnosis, we observed more frequent and higher consumption of all three drug classes. The association between consumption and risk of subsequent CVID diagnosis was statistically significant for all drug classes. The association was stronger with higher consumption and shorter time to CVID diagnosis. The fraction of cases compared to the controls redeeming ≥1 prescription of the included drugs during the study period was higher for AB (97% vs 52%), systemic steroids (35% vs 7.4%), and inhaled bronchodilators/glucocorticoids (46% vs 11.7%) (p<0.001). CONCLUSION: CVID patients have significantly higher use of AB, systemic steroids, and inhaled bronchodilators/glucocorticoids in the 3 years preceding CVID diagnosis than controls. Prescribing these drugs in primary healthcare could be an opportunity to consider (proactive) screening for CVID. Further studies are needed to identify optimal prescription cutoffs that could endorse its inclusion in public health policies.

Cardiovascular events in delayed presentation of HIV: the prospective PISCIS cohort study.

Objectives: People with HIV (PWH) have a higher cardiovascular risk than the general population. It remains unclear, however, whether the risk of cardiovascular disease (CVD) is higher in late HIV presenters (LP; CD4 ≤ 350 cells/µL at HIV diagnosis) compared to PWH diagnosed early. We aimed to assess the rates of incident cardiovascular events (CVEs) following ART initiation among LP compared to non-LP. Methods: From the prospective, multicentre PISCIS cohort, we included all adult people with HIV (PWH) initiating antiretroviral therapy (ART) between 2005 and 2019 without prior CVE. Additional data were extracted from public health registries. The primary outcome was the incidence of first CVE (ischemic heart disease, congestive heart failure, cerebrovascular, or peripheral vascular disease). The secondary outcome was all-cause mortality after the first CVE. We used Poisson regression. Results: We included 3,317 PWH [26 589.1 person/years (PY)]: 1761 LP and 1556 non-LP. Overall, 163 (4.9%) experienced a CVE [IR 6.1/1000PY (95%CI: 5.3-7.1)]: 105 (6.0%) LP vs. 58 (3.7%) non-LP. No differences were observed in the multivariate analysis adjusting for age, transmission mode, comorbidities, and calendar time, regardless of CD4 at ART initiation [aIRR 0.92 (0.62-1.36) and 0.84 (0.56-1.26) in LP with CD4 count <200 and 200- ≤ 350 cells/µL, respectively, compared to non-LP]. Overall mortality was 8.5% in LP versus 2.3% in non-LP (p < 0.001). Mortality after the CVE was 31/163 (19.0%), with no differences between groups [aMRR 1.24 (0.45-3.44)]. Women vs. MSM and individuals with chronic lung and liver disease experienced particularly high mortality after the CVE [aMRR 5.89 (1.35-25.60), 5.06 (1.61-15.91), and 3.49 (1.08-11.26), respectively]. Sensitivity analyses including only PWH surviving the first 2 years yielded similar results. Conclusion: CVD remains a common cause of morbidity and mortality among PWH. LP without prior CVD did not exhibit an increased long-term risk of CVE compared with non-LP. Identifying traditional cardiovascular risk factors is essential for CVD risk reduction in this population.

The multidisciplinary approach to eosinophilia.

Eosinophilic granulocytes are normally present in low numbers in the bloodstream. Patients with an increased number of eosinophilic granulocytes in the differential count (eosinophilia) are common and can pose a clinical challenge because conditions with eosinophilia occur in all medical specialties. The diagnostic approach must be guided by a thorough medical history, supported by specific tests to guide individualized treatment. Neoplastic (primary) eosinophilia is identified by one of several unique acquired genetic causes. In contrast, reactive (secondary) eosinophilia is associated with a cytokine stimulus in a specific disease, while idiopathic eosinophilia is a diagnosis by exclusion. Rational treatment is disease-directed in secondary cases and has paved the way for targeted treatment against the driver in primary eosinophilia, whereas idiopathic cases are treated as needed by principles in eosinophilia originating from clonal drivers. The vast majority of patients are diagnosed with secondary eosinophilia and are managed by the relevant specialty-e.g., rheumatology, allergy, dermatology, gastroenterology, pulmonary medicine, hematology, or infectious disease. The overlap in symptoms and the risk of irreversible organ involvement in eosinophilia, irrespective of the cause, warrants that patients without a diagnostic clarification or who do not respond to adequate treatment should be referred to a multidisciplinary function anchored in a hematology department for evaluation. This review presents the pathophysiology, manifestations, differential diagnosis, diagnostic workup, and management of (adult) patients with eosinophilia. The purpose is to place eosinophilia in a clinical context, and therefore justify and inspire the establishment of a multidisciplinary team of experts from diagnostic and clinical specialties at the regional level to support the second opinion. The target patient population requires highly specialized laboratory analysis and therapy and occasionally has severe eosinophil-induced organ dysfunction. An added value of a centralized, clinical function is to serve as a platform for education and research to further improve the management of patients with eosinophilia. Primary and idiopathic eosinophilia are key topics in the review, which also address current research and discusses outstanding issues in the field.

Plasma Human Immunodeficiency Virus 1 RNA and CD4+ T-Cell Counts Are Determinants of Virological Nonsuppression Outcomes With Initial Integrase Inhibitor-Based Regimens: A Prospective RESPOND Cohort Study.

BACKGROUND: There are conflicting data regarding baseline determinants of virological nonsuppression outcomes in persons with human immunodeficiency virus (HIV) starting antiretroviral treatment (ART). We evaluated the impact of different baseline variables in the RESPOND cohort. METHODS: We included treatment-naive participants aged ≥18 who initiated 3-drug ART, in 2014-2020. We assessed the odds of virological suppression (VS) at weeks 48 and 96 using logistic regression. Viral blips, low-level viremia (LLV), residual viremia (RV), and virological failure (VF) rates were assessed using Cox regression. RESULTS: Of 4310 eligible participants, 72% started integrase strand transfer inhibitor (INSTI)-based regimens. At 48 and 96 weeks, 91.0% and 93.3% achieved VS, respectively. At 48 weeks, Kaplan-Meier estimates of rates were 9.6% for viral blips, 2.1% for LLV, 22.2% for RV, and 2.1% for VF. Baseline HIV-1 RNA levels >100 000 copies/mL and CD4+ T-cell counts ≤200/µL were negatively associated with VS at weeks 48 (adjusted odds ratio, 0.51 [95% confidence interval, .39-.68] and .40 [.27-.58], respectively) and 96 and with significantly higher rates of blips, LLV, and RV. CD4+ T-cell counts ≤200/µL were associated with higher risk of VF (adjusted hazard ratio, 3.12 [95% confidence interval, 2.02-4.83]). Results were consistent in those starting INSTIs versus other regimens and those starting dolutegravir versus other INSTIs. CONCLUSIONS: Initial high HIV-1 RNA and low CD4+ T-cell counts are associated with lower rates of VS at 48 and 96 weeks and higher rates of viral blips, LLV, and RV. Low baseline CD4+ T-cell counts are associated with higher VF rates. These associations remain with INSTI-based and specifically with dolutegravir-based regimens. These findings suggest that the impact of these baseline determinants is independent of the ART regimen initiated.

Comparative Analysis of Primary and Monovalent Booster SARS-CoV-2 Vaccination Coverage in Adults with and without HIV in Catalonia, Spain.

People with HIV (PWH) may be more susceptible to SARS-CoV-2 infection and worse clinical outcomes. We investigated the disparity in SARS-CoV-2 vaccination coverage between PWH and those without HIV (PWoH) in Catalonia, Spain, assessing primary and monovalent booster vaccination coverage from December 2021 to July 2022. The vaccines administered were BNT162, ChAdOx1-S, mRNA-127, and Ad26.COV2.S. Using a 1:10 ratio of PWH to PWoH based on sex, age, and socioeconomic deprivation, the analysis included 201,630 individuals (183,300 PWoH and 18,330 PWH). Despite a higher prevalence of comorbidities, PWH exhibited lower rates of complete primary vaccination (78.2% vs. 81.8%, p < 0.001) but surpassed PWoH in booster coverage (68.5% vs. 63.1%, p < 0.001). Notably, complete vaccination rates were lower among PWH with CD4 <200 cells/µL, detectable HIV viremia, and migrants compared to PWoH (p < 0.001, all). However, PWH with CD4 < 200 cells/µL received more boosters (p < 0.001). In multivariable logistic regression analysis of the overall population, a prior SARS-CoV-2 diagnosis, HIV status, migrants, and mild-to-severe socioeconomic deprivation were associated with lower primary vaccination coverage, reflecting barriers to healthcare and vaccine access. However, booster vaccination was higher among PWH. Targeted interventions are needed to improve vaccine coverage and address hesitancy in vulnerable populations.

Mortality and immunovirological outcomes in patients with advanced HIV disease on their first antiretroviral treatment: differential impact of antiretroviral regimens.

OBJECTIVES: To assess the clinical and immunovirological outcomes among naive patients with advanced HIV presentation starting an antiretroviral regimen in real-life settings. METHODS: This was a multicentre, prospective cohort study. We included all treatment-naive adults with advanced HIV disease (CD4+ T cell count < 200 cells/mm3or presence of an AIDS-defining illness) who started therapy between 2010 and 2020. The main outcomes were mortality, virological effectiveness (percentage of patients with viral load of ≤50 copies/mL) and immune restoration (percentage of patients with CD4+ T cell count above 350 cells/mm3). Competing risk analysis and Cox proportional models were performed. A propensity score-matching procedure was applied to assess the impact of the antiretroviral regimen. RESULTS: We included 1594 patients with advanced HIV disease [median CD4+T cell count of 81 cells/mm3and 371 (23.3%) with AIDS-defining illness] and with a median follow-up of 4.44 years. The most common ART used was an integrase strand transfer inhibitor (InSTI) regimen (46.9%), followed by PI (35.7%) and NNRTI (17.4%), with adjusted mortality rates at 3 years of 3.1% (95% CI 1.8%-4.3%), 4.7% (95% CI 2.2%-7.1%) and 7.6% (95% CI 5.4%-9.7%) (P = 0.001), respectively. Factors associated with increased mortality included older age and history of injection drug use, whilst treatment with an InSTI regimen was a protective factor [HR 0.5 (95% CI 0.3-0.9)]. A sensitivity analysis with propensity score procedure confirms these results. Patients who started an InSTI achieved viral suppression and CD4+ T cell count above 350 cells/mm3significantly earlier. CONCLUSIONS: In this large real-life prospective cohort study, a significant lower mortality, earlier viral suppression and earlier immune reconstitution were observed among patients with advanced HIV disease treated with InSTIs.

Strongyloides stercoralis hyperinfection syndrome with cerebral involvement.

Strongyloidiasis is a disease caused by the intestinal helminth Strongyloides stercoralis When the immune system of infected individuals is compromised, larvae may migrate from the gastrointestinal tract to other tissues, causing S. stercoralis hyperinfection syndrome, which has a reported mortality of 71%. In this case, we report a patient with S. stercoralis hyperinfection syndrome with central nervous system (CNS) involvement. An elderly South East Asian male tourist presented with pulmonary symptoms, fever and infiltrates on chest X-ray. He later developed symptoms of CNS infection. S. stercoralis larvae were found in a stool sample. Microbiological examination of cerebrospinal fluid revealed S. stercoralis-specific DNA. The patient was treated with oral and rectal ivermectin and albendazole. The condition was complicated by sepsis, bacteraemia and hypereosinophilia. Unfortunately, the patient eventually died from pulmonary oedema and insufficiency. This case highlights the global importance of Strongyloides CNS infection in endemic and non-endemic regions.

Determinants of long-term survival in late HIV presenters: The prospective PISCIS cohort study.

Background: Late HIV diagnosis (i.e CD4≤350 cells/µL) is associated with poorer outcomes. However, determinants of long-term mortality and factors influencing immune recovery within the first years after antiretroviral treatment (ART) initiation are poorly defined. Methods: From PISCIS cohort, we included all HIV-positive adults, two-year survivors after initiating ART between 2005-2019. The primary outcome was all-cause mortality according to the two-year CD4 count. We used Poisson regression. The secondary outcome was incomplete immune recovery (i.e., two-year CD4<500 cells/µL). We used logistic regression and propensity score matching. Findings: We included 2,719 participants (16593·1 person-years): 1441 (53%) late presenters (LP) and 1278 non-LP (1145 non-LP with two-year CD4 count >500 cells/µL, reference population). Overall, 113 patients (4·2%) died. Mortality was higher among LP with two-year CD4 count 200-500 cells/µL (aMRR 1·95[95%CI:1·06-3·61]) or <200 cells/µL (aMRR 4·59[2·25-9·37]).Conversely, no differences were observed in participants with two-year CD4 counts >500 cells/µL, regardless of being initially LP or non-LP (aMRR 1·05[0·50-2·21]). Mortality rates within each two-year CD4 strata were not affected by the initial CD4 count at ART initiation (test-interaction, p = 0·48). The stronger factor influencing immune recovery was the CD4 count at ART initiation. First-line integrase-inhibitor-(INSTI)-based regimens were associated with reduced mortality compared to other regimens (aMRR 0·54[0·31-0·93]) and reduced risk of incomplete immune recovery in LP (aOR 0·70[0·52-0·95]). Interpretation: Two-year immune recovery is a good early predictor of long-term mortality in LP after surviving the first high-risk 2 years. Nearly half experienced a favorable immune recovery with a life expectancy similar to non-LP. INSTI-based regimens were associated with higher rates of successful immune recovery and better survival compared to non-INSTI regimens. Funding: Southern-Denmark University, Danish AIDS-foundation, and Region of Southern Denmark.

A retrospective cohort study of patients with eosinophilia referred to a tertiary centre.

INTRODUCTION: Patients with eosinophilia (an increased number of eosinophilic granulocytes > 0.5 × 108/l in the blood) are encountered in all medical specialties and frequently need thorough workup to identify the eliciting causes and decide whether treatment is indicated. In Denmark, highly specialised centres for eosinophilic diseases or conditions have been established to provide a foundation for the management of complicated cases. Here, we present experiences from such a multidisciplinary centre. METHODS: This was a retrospective study of all patients seen in our tertiary centre for eosinophilia in the 2016-2019 period. RESULTS: Referrals mainly derived from specialised secondary care and to a lesser degree from primary care physicians. Patients were either asymptomatic or exhibited symptoms from up to three organ systems and presented a median eosinophil count of 1.7 × 108/l. Up to eight new clonality analyses or imaging studies per patient were performed after referral. One of these, T-cell receptor analysis, was performed frequently but provided limited information, whereas, e.g., flow cytometry proved more clinically applicable owing to its broader diagnostic range. In total, 51 patients were evaluated and classified as secondary (59%), myeloid neoplasm with PDGFRA rearrangement (2%), idiopathic hypereosinophilic syndrome (31%) and idiopathic hypereosinophilia (8%). CONCLUSION: The value of a multidisciplinary and versatile approach in a highly specialised centre has a positive impact on diagnostic processes as well as on the evaluation of treatment need. FUNDING: none. TRIAL REGISTRATION: not relevant.

Tuberculosis incidence and mortality in people living with human immunodeficiency virus: a Danish nationwide cohort study.

OBJECTIVES: To explore changes over time in the epidemiology of tuberculosis (TB) in Denmark in people living with human immunodeficiency virus (HIV) (PLWH). METHODS: In this nationwide, population-based cohort study we included all adult PLWH from the Danish HIV Cohort Study (1995-2017) without previous TB. We estimated TB incidence rate (IR), all-cause mortality rate (MR), associated risk and prognostic factors using Poisson regression. RESULTS: Among 6982 PLWH (73 596 person-years (PY)), we observed 217 TB events (IR 2.9/1000 PY, 95% CI 2.6-3.4: IR 6.7, 95% CI 5.7-7.9 among migrants and IR 1.4, 95% CI 1.1-1.7 among Danish-born individuals; p < 0.001). The IR of concomitant HIV/TB remained high and unchanged over time. The IR of TB diagnosed >3 months after HIV diagnosis declined with calendar time, longer time from HIV diagnosis, and CD4 cell recovery. Independent TB risk factors were African/Asian/Greenland origin (adjusted incidence rate ratio (aIRR) 5.2, 95% CI 3.5-7.6, aIRR 6.5, 95% CI 4.2-10.0, aIRR 7.0, 95% CI 3.4-14.6, respectively), illicit drug use (aIRR 6.9, 95% CI 4.2-11.2), CD4 <200 cells/µL (aIRR 2.7, 95% CI 2.0-3.6) and not receiving antiretroviral therapy (aIRR 3.7, 95% CI 2.5-5.3). Fifty-five patients died (MR 27.9/1000 PY, 95% CI 21.4-36.3), with no improvement in mortality over time. Mortality prognostic factors were Danish-origin (adjusted mortality rate ratio (aMRR) 2.3, 95% CI 1.3-4.3), social burden (aMRR 3.9, 95% CI 2.2-7.0), CD4 <100 cells/µL at TB diagnosis (aMRR 2.6, 95% CI 1.3-4.9), TB diagnosed >3 months after HIV versus concomitant diagnosis (aMRR 4.3, 95% CI 2.2-8.7) and disseminated TB (aMRR 3.3, 95% CI 1.1-9.9). CONCLUSION: Late HIV presentation with concomitant TB remains a challenge. Declining TB rates in PLWH were observed over time and with CD4 recovery, highlighting the importance of early and successful antiretroviral therapy. However, MR remained high. Our findings highlight the importance of HIV and TB screening strategies and treatment of latent TB in high-risk groups.

Incidence of Sexually Transmitted Infections After Initiating HIV Pre-Exposure Prophylaxis Among MSM in Southern Denmark.

Pre-exposure prophylaxis (PrEP) is a new preventive treatment for individuals at high-risk for HIV infection, such as men who has sex with men (MSM). Studies have confirmed the efficacy but concerns about the potential induction of risk compensation remains. We aimed to assess the incidence of sexually transmitted infections (STIs) after PrEP initiation as a proxy for sexual risk behavior.This case-crossover study used data from medical records and from the Danish Microbiology Database from patients who initiated PrEP at the Region of Southern Denmark between 2017 and 2019. Poisson regression was used to assess STI incidence 6 months after PrEP initiation versus the 6 months before. To identify potential risk factors, we compared individuals with an increased STI incidence after PrEP initiation with those without, using logistic regression.In total, 46 MSM initiated PrEP in the study period. We found a significant increase in the number of positive samples for STI after PrEP initiation (IRR 1.83; 95% CI [1.03, 3.26]) and a tendency for higher incidence of STI episodes (1.67; 95% CI [0.91, 3.13]). The increase was concentrated to a group of users, but no significant correlation was found between increasing incidence and the baseline factors examined.We observed a degree of risk compensation after the implementation of PrEP among MSM, clustering to a group of users. Our results highlight the importance of frequent STI screening among MSM on PrEP as timely diagnosis could contribute to an overall decrease in STI incidence and incidence among MSM.

Arcobacter butzleri is an opportunistic pathogen: recurrent bacteraemia in an immunocompromised patient without diarrhoea.

INTRODUCTION: Arcobacter butzleri is attracting increasing interest due to its possible pathogenic properties. Researchers have described cases in which A. butzleri is isolated in stool samples from patients with gastrointestinal symptoms, mostly diarrhoea. The relevance of adding our case to the literature lies in its description of recurrent A. butzleri bacteraemia in a patient without diarrhoea. CASE PRESENTATION: An immunocompromised patient was hospitalized three times within 12 months due to A. butzleri-induced bacteraemia. At no time did the patient experience diarrhoea even though examination of stool samples showed growth of A. butzleri . The isolate was susceptible to gentamicin, colistin and tetracyclines. The patient was successfully treated with doxycycline. CONCLUSION: For the first time in the literature we describe recurrent A. butzleri bacteraemia in a patient without diarrhoea. This case supports the classification of A. butzleri as an opportunistic pathogenic species, which clinical microbiology laboratories should be able to identify.

Prescription of antimicrobials in primary health care as a marker to identify people living with undiagnosed HIV infection, Denmark, 1998 to 2016.

BackgroundDevelopment of additional diagnostic strategies for earlier HIV diagnosis are needed as approximately 50% of newly diagnosed HIV-infected individuals continue to present late for HIV care.AimWe aimed to analyse antimicrobial consumption in the 3 years preceding HIV diagnosis, assess whether there was a higher consumption in those diagnosed with HIV compared with matched controls and whether the level of consumption was associated with the risk of HIV infection.MethodsWe conducted a nested case-control study, identifying all individuals (n = 2,784 cases) diagnosed with HIV in Denmark from 1998 to 2016 and 13 age-and sex-matched population controls per case (n = 36,192 controls) from national registers. Antimicrobial drug consumption was estimated as defined daily doses per person-year. We used conditional logistic regression to compute odds ratios and 95% confidence intervals.ResultsIn the 3 years preceding an HIV diagnosis, we observed more frequent and higher consumption of antimicrobial drugs in cases compared with controls, with 72.4% vs 46.3% having had at least one prescription (p < 0.001). For all antimicrobial classes, the association between consumption and risk of subsequent HIV diagnosis was statistically significant (p < 0.01). The association was stronger with higher consumption and with shorter time to HIV diagnosis.ConclusionHIV-infected individuals have a significantly higher use of antimicrobial drugs in the 3 years preceding HIV diagnosis than controls. Prescription of antimicrobial drugs in primary healthcare could be an opportunity to consider proactive HIV testing. Further studies need to identify optimal prescription cut-offs that could endorse its inclusion in public health policies.

How to Identify Common Variable Immunodeficiency Patients Earlier: General Practice Patterns.

PURPOSE: Diagnostic delay is a major problem concerning common variable immunodeficiency (CVID). We aimed to determine the pattern of general practitioner (GP) consultations in individuals diagnosed with CVID within 3 years before the diagnosis and whether the risk of diagnosis was associated with the frequency of consultations or character of examinations. METHODS: We conducted a nested case-control study, identifying 132 adult CVID patients and 5940 age- and gender-matched controls from national registers during 1997-2013. We used conditional logistic regression to calculate the odds ratios (OR) and 95% confidence intervals (95%CI). RESULTS: The median number of consultations among individuals with CVID was more than twice that of the controls in all 3 years (3rd, 10; 2nd, 11.5; and 1st, 15.4 vs. 4). We found a statistically significant association between the number of consultations and the risk of a subsequent CVID diagnosis, independent of age and gender, but strongest in the individuals < 40 years. In the 3rd year before diagnosis, having 9-15 consultations compared with 1-4 was associated with an OR (95%CI) of 5.0 (2.3-10.9), 2.4 (1.1-5.4), and 1.3 (0.3-5.3) for those aged 18-40, 41-60, and > 60, respectively. Several examinations (i.e., blood tests for inflammation/infection and pulmonary function test) were associated with increased odds of a subsequent CVID diagnosis. CONCLUSION: The risk of a CVID diagnosis was highly related to both the number of consultations and the character of examinations performed by the GP. CVID should be a differential diagnosis among patients with multiple consultations, especially in patients < 40 years old.

Incidence, clinical presentation, and outcome of HIV-1-associated cryptococcal meningitis during the highly active antiretroviral therapy era: a nationwide cohort study.

BACKGROUND: Human immunodeficiency virus (HIV) infection with advanced immunosuppression predisposes to cryptococcal meningitis (CM). We describe the incidence, clinical presentation, and outcome of CM in HIV-infected individuals during the highly active antiretroviral therapy (HAART) era. METHODS: A nationwide, population-based cohort of HIV-infected individuals was used to estimate incidence and mortality of CM including risk factors. A description of neurological symptoms of CM at presentation and follow-up in the study period 1995-2014 was included in this study. RESULTS: Among 6,351 HIV-infected individuals, 40 were diagnosed with CM. The incidence rates were 3.7, 1.8, and 0.3 per 1000 person-years at risk in 1995-1996, 1997-1999, and 2000-2014, respectively. Initiation of HAART was associated with decreased risk of acquiring CM [incidence rate ratio (IRR), 0.1 (95% CI, 0.05-0.22)]. African origin was associated with increased risk of CM [IRR, 2.05 (95% CI, 1.00-4.20)]. The main signs and symptoms at presentation were headache, cognitive deficits, fever, neck stiffness, nausea, and vomiting. All individuals diagnosed with CM had a CD4+ cell count <200 cells/µl [median 26; interquartile range (IQR), 10-50)]. Overall, mortality following CM was high and mortality in the first 4 months has not changed substantially over time. However, individuals who survived generally had a favorable prognosis, with 86% (18/21) returning to the pre-CM level of activity. CONCLUSION: The incidence of HIV-associated CM has decreased substantially after the introduction of HAART. To further decrease CM incidence and associated mortality, early HIV diagnosis and HAART initiation seems crucial.