Beyond the First Year: Epidemiology and Management of Late-Onset Opportunistic Infections After Kidney Transplantation.

Late opportunistic infections (OI) occurring beyond the first year after kidney transplantation (KT) are poorly described and not targeted by prophylactic strategies. We performed a ten-year retrospective monocentric cohort study describing epidemiology, risk factors and impact of late OI occurring 1 year after KT. We included clinically symptomatic OI requiring treatment besides BK virus nephropathy. Control groups included early OI occurring in the first year after KT, and KT recipients without OI since KT and alive with a functional allograft at 1 year. Among 1066 KT recipients, 185 (19.4%) presented a first episode of OI 21.0 (8.0-45.0) months after KT: 120 late OI (64.9%) and 65 early OI (35.1%). Late OI were mainly viral (N = 83, 69.2%), mostly herpes zoster (HZ) (N = 36, 43.4%). Pneumocystis represented most late fungal infections (N = 12/25, 48%). Compared to early OI, we reported more pneumocystis (p = 0.002) and less invasive aspergillosis (p = 0.01) among late OI. Patients with late OI were significatively younger at KT (54.0 ± 13.3 vs. 60.2 ± 14.3 years, p = 0.05). Patient and allograft survival rates between late OI and control groups were similar. Only age was independently associated with mortality. While late OI were not associated with higher mortality or graft loss, implementing prophylactic strategies might prevent such infections.

Risk of infection in patients with hidradenitis suppurativa on biologics or other immunomodulators: a systematic review and meta-analysis.

Hidradenitis suppurativa (HS) is a painful skin condition that significantly affects patients' quality of life. Biologic agents, including anti-TNF agents and IL-17 inhibitors, have shown promise as treatment options for HS. However, there is concern about the increased risk of infections associated with these therapies. We conducted a systematic review and meta-analysis following PRISMA and MOOSE guidelines. We searched PubMed and Embase until February 1, 2023. The primary outcome of interest was the incidence of any infectious complications. Secondary outcomes included serious and opportunistic infections in HS patients treated with biologics or other immunomodulators. Twenty-four studies met our inclusion criteria, comprising 1,696 patients. The pooled incidence rate for any infection was 24.2%, primarily consisting of mild respiratory and skin infections. Subgroup analysis based on the mechanism of action (MOA) showed a pooled incidence of 7.77% for anti-IL1, 14.24% for anti-PDE4, and 21.96% for anti-TNF. Notably, patients receiving anti-IL17 had the highest incidence rate of infection at 33.6%, but the relative risk compared to placebo was not significantly elevated (0.99, 95% CI: 0.86-1.14). Serious infections were rare, with pooled incidences of 0.39% for anti-IL17 and 0.03% for anti-TNF. Opportunistic infections were infrequent, with 10 reported cases, including eight oral candidiasis, one cryptosporidiosis, and one Blastocystis hominis infection. The use of biologic therapies in HS patients does not significantly increase the risk of infectious complications. Additionally, the occurrence of serious or opportunistic infections in HS patients treated with biologics appears to be minimal.

Infection outcomes in patients with rheumatoid arthritis treated with abatacept and other disease-modifying antirheumatic drugs: Results from a 10-year international post-marketing study.

OBJECTIVE: To evaluate risk of infections requiring hospitalization and opportunistic infections, including tuberculosis, in patients with rheumatoid arthritis (RA) treated with abatacept versus conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) and other biologic/targeted synthetic (b/ts) DMARDs. METHODS: Five international observational data sources were used: two biologic registries (Sweden, Germany), a disease registry (USA) and two healthcare claims databases (Canada, USA). Crude incidence rates (IRs) per 1000 patient-years, with 95 % CIs, were used to estimate rate ratios (RRs) comparing abatacept versus csDMARDs or other b/tsDMARDs. RRs were adjusted for demographic factors, comorbidities, and other potential confounders and then pooled across data sources using a random effects model (REM). RESULTS: The data sources included 6450 abatacept users, 136,636 csDMARD users and 54,378 other b/tsDMARD users, with a mean follow-up range of 2.2-6.2 years. Across data sources, the IRs for infections requiring hospitalization ranged from 16 to 56 for abatacept, 19-46 for csDMARDs, and 18-40 for other b/tsDMARDs. IRs for opportunistic infections were 0.4-7.8, 0.3-4.3, and 0.5-3.8; IRs for tuberculosis were 0.0-8.4, 0.0-6.0, and 0.0-6.3, respectively. The pooled adjusted RR (95 % CI), only reported for infections requiring hospitalization, was 1.2 (0.6-2.2) for abatacept versus csDMARDs and 0.9 (0.6-1.3) versus other b/tsDMARDs. CONCLUSIONS: Data from this international, observational study showed similar hospitalized infection risk for abatacept versus csDMARDs or other b/tsDMARDs. IRs for opportunistic infections, including tuberculosis, were low. These data are consistent with the known safety profile of abatacept.

Opportunistic Infections in Patients Receiving Post-Transplantation Cyclophosphamide: Impact of Haploidentical versus Unrelated Donor Allograft.

Post-transplantation cyclophosphamide (PTCy) is an effective strategy for graft-versus-host disease (GVHD) prophylaxis and is the standard of care for haploidentical hematopoietic cell transplantation (HCT). It is increasingly used for matched and mismatched unrelated donor (MUD/MMUD) HCT, but infections remain a concern. The objective of this study was to evaluate the characteristics and risk factors for infections in haploidentical and unrelated donor HCT recipients treated with PTCy-based GVHD prophylaxis. This single-center retrospective study examined 354 consecutive adults undergoing HCT with PTCy-based GVHD prophylaxis (161 MUD/MMUD; 193 haploidentical) between 2015 and 2022. Opportunistic infections (OIs), including cytomegalovirus (CMV), adenovirus (AdV), Epstein-Barr virus (EBV), and invasive fungal disease (IFD), were assessed from day 0 through day +365. The 1-year cumulative incidence functions of OIs and nonrelapse mortality (NRM) were calculated using dates of relapse and repeat HCT as competing risks. Secondary analysis evaluated risk factors for OIs and NRM using univariate and multivariable Cox regression models. Haploidentical HCT recipients had an increased risk of OIs compared to unrelated donor allograft recipients (39% for haploidentical versus 25% for MUD/MMUD; hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.16 to 2.49; P = .006). On multivariable analysis, haploidentical donor (HR, 1.50; 95% CI, 1.01 to 2.23; P = .046), prior HCT (HR, 1.99; 95% CI, 1.29 to 3.09; P = .002), and diagnosis of aGVHD (HR, 1.47; 95% CI, 1.02 to 2.14; P = .041) were associated with increased risk of OIs. NRM within the first year was not significantly different between the 2 cohorts (HR, 1.11; 95% CI, .64 to 1.93; P = .70). Overall, haploidentical donor was a significant risk factor for OIs in patients receiving PTCy, although 1-year NRM was not different between haploidentical HCT and MUD/MMUD HCT recipients. CMV and AdV infections were significantly increased among haploidentical HCT recipients, whereas the incidences of EBV infection and IFD were similar in the 2 cohorts. Our findings may have implications for infection monitoring and prophylaxis in the setting of PTCy, particularly in haploidentical HCT recipients.

Comparative risk of infections between JAK inhibitors versus TNF inhibitors among patients with rheumatoid arthritis: a cohort study.

BACKGROUND: To compare infectious risk between JAK inhibitors (JAKis) versus TNF inhibitors (TNFis) among rheumatoid arthritis (RA) patients in Korea. METHODS: Using 2009-2019 Korea National Health Insurance Service database, we conducted a cohort study on RA patients initiating a JAKi or TNFi. The primary outcomes were herpes zoster (HZ), serious bacterial (SBI), and opportunistic infections (OI). Propensity-score fine-stratification (PSS) and weighting were applied to adjust for > 70 baseline covariates. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models comparing JAKi versus TNFi users. RESULTS: We included 2963 JAKi initiators PSS-weighted on 5169 TNFi initiators. During a follow-up of 1.16 years, the most frequent type of infections was HZ with incidence rate (IR) per 100 person-years of 11.54 and 4.88 in JAKi and TNFi users, respectively. The IR of SBI was 1.39 and 1.32, respectively. The OI was rare with a majority being tuberculosis and showed an IR of 0.11 and 0.49 in JAKi and TNFi users, respectively. The PSS-weighted HR (95% CI) for individual types of infections was 2.37 (2.00-2.80) for HZ, 1.04 (0.71-1.52) for SBI, and 0.25 (0.09-0.73) for OI. CONCLUSIONS: This population-based cohort study on RA patients treated with JAKi or TNFi in Korea showed an exceptionally high IR of HZ in both treatment groups compared to that from Western countries, with an approximately doubled risk associated with JAKi versus TNFi use. The risk of SBI was comparable, but the risk of OI, particularly tuberculosis, was less among JAKi than TNFi initiators.

Distribution pattern and prevalence of opportunistic infections and their possible reciprocal effects among HIV patients, Burayu health centers, Ethiopia.

INTRODUCTION: Opportunistic infections are a major public health problems in immuno-compromised individuals, particularly in HIV patients, and form a lethal combination, each speeding the progress of the other. The aim of this study was to assess the pattern and prevalence of opportunistic infections and their reciprocal effects among HIV patients attending the Burayu Health Centers. METHODOLOGY: A health institution-based retrospective cross-sectional study was conducted on 1,448 HIV patients. All patients diagnosed with HIV and HIV-opportunistic co-infections with complete data were included. Logistic regression analysis was used to quantify the association of HIV-opportunistic co-infections and various socio-demographic and clinical variables. RESULTS: A total of 1,448 HIV- positive patients were reviewed and 572 (39.5%) were found to have opportunistic infections. The trend of HIV co-infection showed gradually decreased. Majority of HIV patients were found at a CD4+ count < 200cells/mm3.The rate of opportunistic infections increased with decreasing CD4 T-cell count. HIV-infected patients with a CD4+ cell count of < 200 cells/mm3 were found to be 44 times more likely to develop opportunistic infections. HIV-opportunistic co-infection was significantly associated with sex, marital status, ART drug adherence, residence, and educational status of the patients. The odds of co-infections in patients who were urban dwellers were 2 times higher than in those who lived in rural areas. Similarly, patients who were single were 3 times more likely to be infected with coinfections. Maleness was found to be protective from coinfection and it showed a reduction of 64%. CONCLUSIONS: Opportunistic co-infections are more prevalent in HIV-infected patients with a CD4+ cell count of < 200 cells/mm3, poor drug adherence, and also associated with the occupation. So, regular examination and appropriate medication can reduce the prevalence of opportunistic co-infections.

Clinical Course, Nosocomial, and Opportunistic Infections Among Kidney Transplant Recipients with COVID-19: A Retrospective Single Center Study.

BACKGROUND: We report the results of an observational study, analyzing the clinical course of kidney transplant patients hospitalized for COVID-19 and comparing it with a control to determine if outcomes, nosocomial, and opportunistic infections were different between groups. METHODS: An observational, retrospective, case-control, single-center study, including a group of kidney transplant adults diagnosed with COVID-19, from March 2020 to April 2022. Transplant patients hospitalized for COVID-19 comprised the cases. The control group consisted of non-transplanted adults, without immunosuppressive treatment, hospitalized for COVID-19, and matched by age, sex, and month at diagnosis of COVID-19. Study variables were collected, including demographic/clinical, epidemiologic, clinical/biological at diagnosis, evolutive, and outcome variables. RESULTS: Fifty-eight kidney transplant recipients were included. Thirty required hospital admission. Ninety controls were included. Transplant recipients had a higher frequency of intensive care unit (ICU) admission, ventilatory support, and death. The relative risk for death was 2.45. When adjusted by baseline estimated glomerular filtration rate (eGFR) and comorbidity, only the risk for opportunistic infection remained high. Variables independently associated with death were dyslipidemia, eGFR at admission, MULBSTA score, and ventilatory support. Pneumonia by Klebsiella oxytoca was the most frequent nosocomial infection. Pulmonary aspergillosis was the most frequent opportunistic infection overall. Pneumocystosis and cytomegalovirus colitis were more frequent among transplant patients. The relative risk for opportunistic infection in this group was 1.88. Baseline eGFR, serum interleukin 6 level, and coinfection were independently associated with it. CONCLUSIONS: Evolutive course of COVID-19 requiring hospitalization in renal transplant recipients was primarily determined by comorbidity and baseline kidney function. At equal comorbidity and renal function, there were no differences in mortality, ICU admission, nosocomial infection, and hospital stay. However, the risk for opportunistic infection remained high.

Incidence of opportunistic infections and its predictors among HIV/AIDS patients on antiretroviral therapy in Gondar University Comprehensive and Specialized Hospital, Ethiopia.

Introduction: Opportunistic infections (OIs) are the leading cause of morbidity and mortality among adults living with HIV. Current and accurate information about the occurrence of opportunistic infections in HIV-infected adults is critical for developing more effective treatments and interventions. However, few studies have been conducted in Ethiopia on the prevalence of common opportunistic infections in HIV-infected adults. Thus, the purpose of this study was to determine the prevalence and predictors of opportunistic infections among HIV-infected adults receiving antiretroviral therapy (ART) at the comprehensive specialized hospital affiliated with the University of Gondar.Methods: Between January 11, 2015, and January 10, 2021, a retrospective cohort study was conducted at the University of Gondar comprehensive specialized hospital. A total of 715 HIV-infected adults on ART were included in the study. Data were extracted from the charts of HIV-infected adults using a data extraction form adapted from the ART entry and follow-up forms. Epi-dataTM Version 4.5 was used to enter data, and StataTM Version 16 was used to analyze the data. The time interval between opportunistic infections was estimated using the Kaplan Meier survival curve. To identify risk predictors of opportunistic infections, bivariate and multivariate semi-parametric and parametric regression models were fitted.Result: This study included the records of 715 HIV-infected adults-initiated ART between January 11, 2015, to January 10, 2021. During the follow-up period, the overall incidence of opportunistic infections was 4.1 (95 percent CI 3.74 to 4.44) per 10,000 person-year observation, with a median of 57 months (IQR = 40-69 months). Pneumocystis' pneumonia at 90(16.51%) was the most encountered OI at follow-up. Adults are presenting with baseline CD4 < 200 cells/µl counts (AHR = 1.41, 95% CI 1.18 to 1.69), bedridden baseline functional status (AHR = 1.35, 95% CI 1.01 to 1.82), WHO clinical stage II (AHR = 5.87, 95% CI 3.97 to 8.69) and WHO clinical stage III (AHR = 5.85, 95% CI 3.55 to 9.65) were notably associated with the incidence of opportunistic infections development.Conclusions: Opportunistic infections are uncommon among HIV-infected adults in this study. In terms of predictors, such as a low CD4 count and an advanced WHO stage (II or III), bedridden functional status was found to be significantly associated with OIs.

Opportunistic Infections Post-Lung Transplantation: Viral, Fungal, and Mycobacterial.

Opportunistic infections are a leading cause of lung transplant recipient morbidity and mortality. Risk factors for infection include continuous exposure of the lung allograft to the external environment, high levels of immunosuppression, impaired mucociliary clearance and decreased cough reflex, and impact of the native lung microbiome in single lung transplant recipients. Infection risk is mitigated through careful pretransplant screening of recipients and donors, implementation of antimicrobial prophylaxis strategies, and routine surveillance posttransplant. This review describes common viral, fungal, and mycobacterial infectious after lung transplant and provides recommendations on prevention and treatment.

Immunosuppression by opioids: Mechanisms of action on innate and adaptive immunity.

Opioids are excellent analgesics for the clinical treatment of various types of acute and chronic pain, particularly cancer-related pain. Nevertheless, it is well known that opioids have some nasty side effects, including immunosuppression, which is commonly overlooked. As a result, the incidence of opportunistic bacterial and viral infections increases in patients with long-term opioid use. Nowadays, there are no effective medications to alleviate opioid-induced immunosuppression. Understanding the underlying molecular mechanism of opioids in immunosuppression can enable researchers to devise effective therapeutic interventions. This review comprehensively summarized the exogenous opioids-induced immunosuppressive effects and their underlying mechanisms, the regulatory roles of endogenous opioids on the immune system, the potential link between opioid immunosuppressive effect and the function of the central nervous system (CNS), and the future perspectives in this field.

Risk of severe and opportunistic infections and the impact of SARS-COV-2 on this risk in a nationwide cohort of patients with inflammatory bowel disease.

BACKGROUND: The Inflammatory Bowel Disease (IBD) patients have adopted lifestyle modifications to prevent infection via SARS COV-2. AIMS: This study aims to examine rate of serious infections and opportunistic infections in the pre-pandemic and pandemic period, and to analyse if the risk associated with medications used to treat IBD were potentially modified by associated change in lifestyle. METHODS: We conducted a retrospective cohort study of patients from the US national Veteran Affairs Healthcare System (VAHS). Patients were stratified into two groups: pre-pandemic (prior to SARS COV-2 pandemic) and pandemic (during SARS COV-2 pandemic) and outcomes were measured in these groups. Primary outcome was occurrence of any serious infection. Secondary outcome was occurrence of any opportunistic infection. RESULTS: There were 17,202 IBD patients in the pre-pandemic era and 15,903 patients in the pandemic era. The pre-pandemic era had a significantly higher proportion of serious infections relative to the pandemic era (5.1% vs. 4.4%, p = 0.002). The proportion of opportunistic infections were similar between pre-pandemic and pandemic eras (0.3% vs. 0.3%, p = 0.82). Relative to 5-ASA, patients taking anti-TNF (HR = 1.50 (1.31-1.72)), anti-TNF+TP (HR = 1.56 (1.24-1.95)) or vedolizumab (HR = 1.81 (1.49-2.20)) had an increased hazard of serious infection (p > 0.001). CONCLUSION: In a nationwide cohort of IBD patients, we found that risk of serious infections could possibly be affected by behavioural modifications due to SARS-COV-2 pandemic.

HIV and COVID-19 Disease.

Despite effective antiretroviral therapy (ART), HIV infected individuals throughout the world remain at significant risk of respiratory infections and non-communicable disease. Severe disease from SARS-CoV-2 is associated with a hyperinflammatory phenotype which manifests in the lungs as pneumonia and in some cases can lead to acute respiratory failure. Progression to severe COVID-19 is associated with comorbid disease such as obesity, diabetes mellitus and cardiovascular disease, however data concerning the associated risks of HIV coinfection are still conflicting, with large population studies demonstrating poorer outcomes, whilst smaller, case-controlled studies showing better outcomes. Furthermore, underlying immunopathological processes within the lungs and elsewhere, including interactions with other opportunistic infections (OI), remain largely undefined. Nonetheless, new and repurposed anti-viral therapies and vaccines which have been developed are safe to use in this population, and anti-inflammatory agents are recommended with the caveat that the coexistence of opportunistic infections is considered and excluded. Finally, HIV infected patients remain reliant on good ART adherence practices to maintain HIV viral suppression, and some of these practices were disrupted during the COVID-19 pandemic, putting these patients at further risk for acute and long-term adverse outcomes.

Opportunistic Infections in Patients with Inflammatory Bowel Disease Treated with Advanced Therapies: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND AIMS: Advanced therapies for inflammatory bowel disease [IBD] could potentially lead to a state of immunosuppression with an increased risk of opportunistic infections [OIs]. We aimed to provide an update on the incidence of OIs among adult IBD patients in randomized controlled trials [RCTs] of approved biologics and small-molecule drugs [SMDs]. Also, we aimed to describe OI definitions utilized in RCTs, to ultimately propose a standardized definition. METHODS: Electronic databases were searched from January 1, 1990, until April 16, 2022. Our primary outcome was incidence rate of overall OIs among IBD patients exposed and unexposed to biologics or SMDs. We also describe specific OIs reported in included trials, as well as definitions of OIs within studies when provided. RESULTS: Ninety studies were included. The incidence rates of reported OIs were 0.42 and 0.21 per 100 person-years in patients exposed to advanced therapies and placebo, respectively. This was highest for anti-tumour necrosis factors [0.83 per 100 person-years] and Janus kinase inhibitors [0.55 per 100 person-years] and lowest for anti-integrins and ozanimod. On meta-analysis, no increased risk of OIs was observed. None of the studies provided a detailed definition of OIs, or a comprehensive list of infections considered as OIs. CONCLUSION: Different mechanisms of action may have specific OI profiles. In the absence of a uniform definition of OIs, these estimates are less reliable. We propose a definition to be used in future studies to help provide standardized reporting. When using this definition, we saw significant differences in incidence rates of OIs across mechanisms of action.

Tofacitinib for the Treatment of Ulcerative Colitis: An Integrated Summary of up to 7.8 Years of Safety Data from the Global Clinical Programme.

BACKGROUND AND AIMS: Tofacitinib is an oral small molecule Janus kinase [JAK] inhibitor for the treatment of ulcerative colitis. We report an integrated summary of tofacitinib safety [exposure: ≤7.8 years] from the global clinical programme. METHODS: Patients receiving tofacitinib 5 or 10 mg twice daily [BID] from completed phase [P]2/3 placebo-controlled studies, an open-label, long-term extension study [final data cut-off: August 24, 2020], and interim analysis of a P3b/4 study (interim data cut-off: February 20, 2020; Overall plus P3b/4 [2020] Cohort) were included. Proportions with adverse events [AEs] and serious AEs, and incidence rates [IRs; unique patients with events/100 patient-years] for deaths and AEs of special interest [AESI] were evaluated. Opportunistic infections, malignancies, major adverse cardiovascular events [MACE] and gastrointestinal perforations were adjudicated. RESULTS: In total, 1157 patients received one or more dose of tofacitinib (mean duration: 946.9 days); 955/1157 [83%] received a predominant dose of 10 mg BID; 412/1157 [35.6%] received tofacitinib for >4 years; 992/1157 [85.7%] had AEs, 244/1157 [21.1%] had serious AEs and 134/1157 (11.6%) discontinued use due to AEs. IRs [95% confidence intervals] for all tofacitinib doses were: deaths, 0.23 [0.09-0.46]; serious infections, 1.69 [1.26-2.21]; herpes zoster [non-serious and serious], 3.30 [2.67-4.04]; opportunistic infections, 1.03 [0.70-1.46]; malignancies (excluding non-melanoma skin cancer [NMSC]), 0.84 [0.55-1.24]; NMSC, 0.73 [0.45-1.10]; MACE, 0.29 [0.13-0.55]; deep vein thrombosis, 0.03 [0.00-0.18]; pulmonary embolism, 0.19 [0.07-0.42]; gastrointestinal perforations, 0.10 [0.02-0.28]. CONCLUSIONS: AESI IRs were stable to 7.8 years and generally <2.0 in the Overall plus P3b/4 [2020] Cohort, with the exception of herpes zoster [a known risk of tofacitinib treatment]. ClinicalTrials.gov:NCT00787202;NCT01465763;NCT01458951;NCT01458574;NCT01470612;NCT03281304JCC Topic/keyword selection: 3. Clinical trials.

Incidence of opportunistic infections in patients with rheumatoid arthritis treated with different molecular-targeted drugs: A population-based retrospective cohort study.

OBJECTIVES: We compared the incidences of four opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with molecular-targeted drugs from big claims data. MATERIALS AND METHODS: We identified 205,906 patients with RA who were prescribed molecular-targeted drugs in 2010-17 from the National Database of Japan and calculated the incidence of four OIs (Pneumocystis pneumonia, tuberculosis, nontuberculous mycobacterial infection, and herpes zoster). RESULTS: The total number of Pneumocystis pneumonia, tuberculosis, nontuberculous mycobacterial infection, and herpes zoster patients with biological disease-modifying antirheumatic drugs or tofacitinib treatment history in RA was 765, 1158, 834, and 18,336, respectively. The incidence rates of each OI for all biological disease-modifying antirheumatic drugs were 0.14, 0.14, 0.09, and 2.40 per 100 person-years, respectively, while for tofacitinib they were 0.22, 0.22, 0.07, and 7.00 per 100 person-years. No big difference was observed among biological disease-modifying antirheumatic drugs. All OIs showed higher incidence in those >65 years, but Pneumocystis pneumonia, nontuberculous mycobacterial infection, and herpes zoster showed no difference between those 65-74 years old and those >75 years old. The median of occurrence was the third, seventh, ninth, and thirteenth month after treatment, respectively. CONCLUSIONS: We counted real incidence rates of OIs for the whole nation from big claims data.

Opportunistic infections associated with Janus kinase inhibitor treatment for rheumatoid arthritis: A structured literature review.

BACKGROUND: The availability of Janus kinase (JAK) inhibitors has transformed the management of rheumatoid arthritis (RA), helping patients achieve clinical remission. However, the emergence of opportunistic infections (OIs) associated with the use of JAK inhibitors has been reported. This structured literature review was conducted to summarize reports of OIs associated with JAK inhibitor treatment for RA in clinical trials. METHODS: Structured searches were performed in MEDLINE® and Embase® to identify relevant clinical trial data through March 2021. Bibliographic searches of recent reviews were also conducted, and gray literature searches were used to supplement key gap areas. Publications were screened, extracted, and quality assessed. Data were narratively synthesized. RESULTS: Following screening, 105 publications describing 62 unique clinical trials reporting the rates of OIs in RA patients treated with JAK inhibitors were included. Overall, the highest exposure-adjusted incidence rate was reported for herpes zoster (HZ) infection (any form), followed by OI (any) and tuberculosis based on limited data from clinical trials with approved doses of JAK inhibitors. Lack of head-to-head trials and differences in trial design preclude direct comparison across JAK inhibitors. Higher rates of OIs were noted in the Asian and Australian populations compared with the global population. Higher rates of OIs were also noted with increasing dose of JAK inhibitors in most clinical trial data. CONCLUSIONS: HZ was the most common OI reported among RA patients using all currently approved JAK inhibitors in clinical trials, although tuberculosis and other OIs were also reported. More long-term safety studies in the real-world setting are needed to compare the risk of OIs between various JAK inhibitors.

Anemia and opportunistic infections in hospitalized people living with HIV: a retrospective study.

BACKGROUND: There is a high prevalence of anemia among people living with HIV in Guangxi, China. Therefore, we investigated anemia and opportunistic infections in hospitalized people living with HIV and explored the risk factors related to anemia in people living with HIV to actively prevent anemia in people living with HIV. METHODS: We retrospectively studied people living with HIV admitted to Guangxi Chest Hospital from June 2016 to October 2021. Detailed information on the sociodemographic and clinical features of the participants was collected. The X2 test was used to compare the prevalence between the anemic and non-anemic groups. The logistic regression analysis was applied to exclude confounding factors and identify factors related to anemia. RESULTS: Among 5645 patients with HIV, 1525 (27.02%) had anemia. The overall prevalence of mild, moderate, and severe anemia was 4.66%, 14.08%, and 8.27%, respectively. The factors significantly related to increased risk of anemia were CD4 count < 50 cells/µl (aOR = 2.221, 95% CI = [1.775, 2.779]), CD4 count 50-199 cells/µl (aOR = 1.659, 95% CI = [1.327, 2. 073]), female (aOR = 1.644, 95% CI = [1.436, 1.881]) co-infected with HCV (aOR = 1.465, 95% CI = [1.071, 2.002]), PM (aOR = 2.356, 95% CI = [1.950, 2.849]), or TB (aOR = 1.198, 95% CI = [1.053, 1.365]). CONCLUSIONS: Within Guangxi of China, 27.02% of hospitalized people living with HIV presented with anemia. Most patients with anemia were in the mild to moderate stage. The low CD4 count, female gender, and concomitant infection with Penicillium marneffei, Hepatitis C virus, or Tuberculosis were independent correlates of anemia. Thus, these findings would be helpful to clinicians in preventing and intervening in anemia in people living with HIV.

Caracterização das infecções que acometem o usuário no momento do diagnóstico para o Hiv/Aids / Characterization of infections that affect the user at the moment of diagnosis for Hiv/Aids / Caracterización de las infecciones que afectan a los usuarios en el momento del diagnóstico del Vih/Sida

: O estado do Pará, de 2009 a 2019, apresentou um aumento de 46,5% na taxa de detecção de aids. O que destaca a importância de estudos para a avaliação e acompanhamento deste público. Objetivo: Analisar as infecções que acometem os usuários de um centro de referência no momento de seu diagnóstico para a infecção pelo HIV. Métodos: Estudo descritivo, realizado em um centro de referência da cidade de Santarém, Pará. A amostra foi de 332 prontuários de pacientes diagnosticados para o HIV nos anos de 2016 e 2017. A coleta de dados buscou informações sociodemográficas, clínicas e imunológicas dos pacientes no momento do diagnóstico para a infecção pelo HIV. Os dados foram organizados e analisados por estatística descritiva e inferencial, adotando- se p<0,05. Resultados: Observou-se prevalência do sexo masculino (67%), faixa etária de 15-24 anos (32,2%), solteiros (59%), com vínculo empregatício (64,5%), contagem de linfócitos T CD4+ ≥200 céls/mm3 (54,8%) e carga viral detectável (75,3%). A Candidíase (25%) e a Tuberculose (25%) predominaram como infecções oportunistas (IO), e a Sífilis (67,5%) como outras infecções. Conclusão: Conforme método proposto e os dados já informados, conclui-se que o diagnóstico para a Sífilis se associou ao sexo masculino, bem como a situação de contagem de linfócitos T CD4+ <200 céls/mm3 se associou com a presença de alguma infecção oportunista, da instalação da Candidíase e da Tuberculose.

Introduction: The state of Pará, from 2009 to 2019, showed a 46.5% increase in the AIDS detection rate. What stands out the importance of studies for the evaluation and monitoring of this public. Objective: Analyze the infections that affect the users of a reference center at the moment of diagnosis for HIV infection. Methods: Descriptive study, carried out in a reference center in the city of Santarém, Pará. The sample consisted of 332 records of patients diagnosed with HIV in the years 2016 and 2017. The data collection sought sociodemographic, clinical and immunological information of the patients at the moment diagnosis for HIV infection. The data were organized and analyzed using descriptive and inferential statistics, adopting p <0.05. Results: There was a prevalence of males (67%), aged 15-24 years (32.2%), single (59%), with employment (64.5%), CD4 + T lymphocyte count ≥200 cells/mm3 (54.8%) and detectable viral load (75.3%). Candidiasis (25%) and Tuberculosis (25%) predominated as opportunistic infections (IO), and Syphilis (67.5%) as other infections. Conclusion: According to the proposed method and the data already reported, it is concluded that the diagnosis for Syphilis was associated with the male gender, as well as the situation of CD4 + T lymphocyte count <200 cells/mm3 was associated with the presence of some opportunistic infection, of the installation of Candidiasis and Tuberculosis.

Introducción: El estado de Pará, de 2009 a 2019, presentó un aumento del 46,5% en la tasa de detección del SIDA. Lo que pone de manifiesto la importancia de los estudios para la evaluación y el seguimiento de este público. Objetivo: Analizar las infecciones que sufren los usuarios de un centro de referencia en el momento de su diagnóstico de infección por VIH. Métodos: Estudo descritivo, realizado em um centro de referência da cidade de Santarém, Pará. La muestra fue de 332 historias clínicas de pacientes diagnosticados de VIH en los años 2016 y 2017. La recogida de datos buscaba información sociodemográfica, clínica e inmunológica de los pacientes en el momento del diagnóstico de la infección por VIH. Los datos se organizaron y analizaron mediante estadísticas descriptivas e inferenciales, adoptando p<0,05. Resultados: Se observó la prevalencia del sexo masculino (67%), el grupo de edad de 15 a 24 años (32,2%), la soltería (59%), el empleo (64,5%), el recuento de linfocitos T CD4+ ≥200 células/mm3 (54,8%) y la carga viral detectable (75,3%). La candidiasis (25%) y la tuberculosis (25%) predominaron como infecciones oportunistas (IO), y la sífilis (67,5%) como otras infecciones. Conclusión: De acuerdo con el método propuesto y los datos ya informados, se concluye que el diagnóstico de Sífilis se asocia al sexo masculino, así como la situación de contagio de linfocitos T CD4+ <200 células/mm3 se asocia a la presencia de alguna infección oportunista, a la instauración de la Candidiasis y a la Tuberculosis.

The Risk of Opportunistic Infections and the Role of Antibiotic Prophylaxis in Patients on Checkpoint Inhibitors Requiring Steroids.

BACKGROUND: Immune-related adverse events (irAEs) often require treatment with high-dose systemic steroids (SS) and other immunosuppressive agents (ISAs). NCCN Guidelines recommend prophylactic antibiotics for Pneumocystis jirovecii pneumonia (PJP) for patients receiving prolonged SS/ISAs. However, there is a paucity of evidence regarding the incidence of opportunistic infections (OIs) and non-OIs and the role of prophylactic antibiotics in patients on SS/ISAs for irAEs. METHODS: A retrospective analysis was conducted of patients treated using immune checkpoint inhibitor (ICI) therapy at 5 MedStar Health hospitals from January 2011 to April 2018. OIs were defined per the Infectious Diseases Society of America guidelines for the prevention and treatment of OIs in patients with HIV. The study cohort included patients who received ≥20 mg daily of a prednisone equivalent for ≥4 weeks to manage irAEs. RESULTS: The study cohort identified 112 (15%) of 758 total patients treated using ICIs. Baseline characteristics included the following: median age was 64 years, 74% (n=82) of patients were White, 89% (n=100) had an ECOG performance status ≤1, 61% (n=68) had melanoma, 19% (n=21) had non-small cell lung cancer, 45% (n=50) were treated using an anti-PD-(L)1 ICI, and 33% (n=37) were treated using an anti-PD-1/anti-CTLA-4 combination. The median starting SS dose was 100 mg of a prednisone equivalent, and 25% of patients required additional ISAs, with infliximab (n=15) and mycophenolate mofetil (n=9) being the most common. We found that 20% (n=22) of patients developed any infection, including 7% (n=8) with OIs (oral candidiasis [n=4], nondisseminated varicella zoster infection [n=2], PJP [n=1], and Listeria monocytogenes endophthalmitis [n=1]) and 13% (n=14) with non-OIs (most common: Clostridium difficile and pneumonia [n=5 each]). PJP prophylaxis with sulfamethoxazole/trimethoprim was given to 13% (n=14) patients, of whom 43% (n=6) developed OIs/non-OIs. CONCLUSIONS: Our study highlights the fundamental issues for patients on ICI therapy who require SS/ISAs for irAEs: the degree of immunosuppression and the relative risk of OI. We noted a low incidence of OIs overall and breakthrough infections despite PJP prophylaxis. We question whether PJP prophylaxis is efficacious or necessary. Prospective trials are required to answer these questions.

Temporal trends in hospitalisation for opportunistic infections in lupus patients in Western Australia.

BACKGROUND: Lupus patients often require aggressive immunosuppressive therapy, which increases the risk for infections. We studied the temporal rates for opportunistic infections (OI) and associated mortality in lupus patients hospitalised in Western Australia. METHODS: All patients hospitalized in the period 1985-2015 with ≥2 ICD based diagnostic codes for SLE were included. OI was defined as a microbiologically confirmed mycobacterial, fungal, or viral infection. Descriptive data are given as median (IQR) and frequency (%) with incidence rates (IR) calculated per 1000 person years and IR trend rates analysed across 10-year periods by least square regression (R2). RESULTS: The study cohort (n = 1408) contained 85.3% females with age at entry 35 years (IQR 22-51). During median follow-up of 21.1 years (IQR 17.5-29.6) hospitalisation for OI occurred in 121 (8.6%) patients with recurrent or multiple OI observed in 42 (34.7%) patients. During 29.771 thousand person years, a total of 295 OI were diagnosed for an overall IR rate of 9.91 (CI 8.82-11.09)/1000 person years which did not decrease significantly over time (R2 0.14). Significant decreases were however seen in the IR for tuberculosis (R2 0.88), cryptococcal (R2 0.98) and pneumocystis (R2 0.98) infections, with increasing IR observed for other mycobacteria (R2 0.99) and aspergillosis (R2 0.55) and little change seen for H Zoster (R2 0.18) and Varicella (R2 0.10) infections. In-hospital death during OI admission occurred in 9/121 patients (7.4%). There was no significant gender difference in IR or outcome of OI. CONCLUSIONS: Hospitalization rates for OI in lupus patients have not changed significantly over time, but there has been a clear shift in the underlying OI. The decrease in mycobacterial and pneumocystis infections suggest successful prophylaxis but the increase in viral and mycotic infections indicate a sustained need to improve prevention of these OI in lupus patients.