Trends in mortality in people with HIV from 1999 to 2020: a multi-cohort collaboration.

BACKGROUND: Mortality among people with HIV declined with the introduction of combination antiretroviral therapy. We investigated trends over time in all-cause and cause-specific mortality in people with HIV from 1999-2020. METHODS: Data were collected from the D:A:D cohort from 1999 through January 2015 and RESPOND from October 2017 through 2020. Age-standardized all-cause and cause-specific mortality rates, classified using Coding Causes of Death in HIV (CoDe), were calculated. Poisson regression models were used to assess mortality trends over time. RESULTS: Among 55716 participants followed for a median of 6 years (IQR 3-11), 5263 participants died (crude mortality rate [MR] 13.7/1000 PYFU; 95%CI 13.4-14.1). Changing patterns of mortality were observed with AIDS as the most common cause of death between 1999- 2009 (n = 952, MR 4.2/1000 PYFU; 95%CI 4.0-4.5) and non-AIDS defining malignancy (NADM) from 2010 -2020 (n = 444, MR 2.8/1000 PYFU; 95%CI 2.5-3.1). In multivariable analysis, all-cause mortality declined over time (adjusted mortality rate ratio [aMRR] 0.97 per year; 95%CI 0.96, 0.98), mostly from 1999 through 2010 (aMRR 0.96 per year; 95%CI 0.95-0.97), and with no decline shown from 2011 through 2020 (aMRR 1·00 per year; 95%CI 0·96-1·05). Mortality due all known causes except NADM also declined over the entire follow-up period. CONCLUSION: Mortality among people with HIV in the D:A:D and/or RESPOND cohorts decreased between 1999 and 2009 and was stable over the period from 2010 through 2020. The decline in mortality rates was not fully explained by improvements in immunologic-virologic status or other risk factors.

Who is lost to follow-up in HIV care? Assessment of care retention over time and the impact of COVID-19. Longitudinal analysis of the PISCIS cohort.

INTRODUCTION: People living with HIV who are lost to follow-up have a greater risk of health deterioration, mortality, and community transmission. OBJECTIVE: Our aim was to analyse both how rates of loss to follow-up (LTFU) changed between 2006 and 2020 and how the COVID-19 pandemic affected these rates in the PISCIS cohort study of Catalonia and the Balearic Islands. METHODS: We analysed socio-demographic and clinical characteristics of LTFU yearly and with adjusted odds ratios to assess the impact of these determinants on LTFU in 2020 (the year of COVID-19). We used latent class analysis to categorize classes of LTFU based on their socio-demographic and clinical characteristics at each year. RESULTS: In total, 16.7% of the cohort were lost to follow-up at any time in the 15 years (n = 19 417). Of people living with HIV who were receiving follow-up, 81.5% were male and 19.5% were female; of those who were lost to follow-up, 79.6% and 20.4% were male and female, respectively (p < 0.001). Although rates of LTFU increased during COVID-19 (1.11% vs. 0.86%, p = 0.024), socio-demographic and clinical factors were similar. Eight classes of people living with HIV who were lost to follow-up were identified: six for men and two for women. Classes of men (n = 3) differed in terms of their country of birth, viral load (VL), and antiretroviral therapy (ART); classes of people who inject drugs (n = 2) differed in terms of VL, AIDS diagnosis, and ART. Changes in rates of LTFU included higher CD4 cell count and undetectable VL. CONCLUSIONS: The socio-demographic and clinical characteristics of people living with HIV changed over time. Although the circumstances of the COVID-19 pandemic increased the rates of LTFU, the characteristics of these people were similar. Epidemiological trends among people who were lost to follow-up can be used to prevent new losses of care and to reduce barriers to achieve Joint United Nations Programme on HIV/AIDS 95-95-95 targets.

Empirical use of ß-lactam/ß-lactamase inhibitor combinations does not increase mortality compared with cloxacillin and cefazolin in methicillin-susceptible Staphylococcus aureus bacteraemia: a propensity-weighted cohort study.

OBJECTIVES: To evaluate the effectiveness of empirical therapy with ß-lactam/ß-lactamase inhibitor combinations (BL/BLICs) for MSSA bacteraemia. METHODS: We conducted a post hoc analysis of all adult patients with MSSA bacteraemia who were hospitalized at a Spanish university hospital between 2013 and 2018. We compared 30 day mortality among patients receiving initial therapy with BL/BLICs (de-escalated to cloxacillin or cefazolin within 96 h) versus cloxacillin or cefazolin, using propensity score analysis with the inverse probability of treatment weighting (IPTW) method. RESULTS: We evaluated 373 patients with MSSA bacteraemia. Among them, 198 patients met the eligibility criteria, including 127 patients in the BL/BLICs group and 71 patients in the cloxacillin/cefazolin group. Patients in the BL/BLICs group had a higher Charlson comorbidity index (median, 2 [IQR, 1-4.5] versus 2 [IQR, 0-4]); an increased proportion of high-risk sources (i.e. endocarditis, respiratory sources and bacteraemia of unknown origin [34.6% versus 18.3%]); and an earlier start of antibiotic treatment (median, 0 days [IQR, 0-0] versus 1 day [IQR, 1-2]). Thirty day mortality did not significantly differ between the BL/BLICs and the cloxacillin/cefazolin groups (27 patients [21.3%] versus 13 patients [18.3%]; IPTW-adjusted OR = 0.53 [95% CI, 0.18-1.51]). For secondary outcomes, 7 day mortality and 90 day relapse were not statistically different between study groups (8.7% versus 5.6% [P = 0.62] and 6.2% versus 3.8% [P = 0.81], respectively). CONCLUSIONS: BL/BLICs might be an effective empirical treatment for MSSA bacteraemia when de-escalated to cloxacillin or cefazolin within 96 h from the index blood culture.

Effectiveness of trichloroacetic acid versus electrocautery for the treatment of anal high-grade squamous intraepithelial lesions in persons with HIV.

PURPOSE: This study aimed to compare trichloroacetic acid (TCA) versus electrocautery (ECA) for the treatment of anal high-grade squamous intraepithelial lesions (HSIL). METHODS: This is an observational, single-center study. All subjects with HIV who had anal HSIL treated with TCA or ECA from 2010 to 2022 were included. Effectiveness was evaluated by on-treatment analysis, defining response as the resolution of HSIL and recurrence as a new diagnosis of HSILs during follow-up. A propensity score analysis was used to adjust for confounding factors. RESULTS: In total, 227 and 260 HSIL episodes were treated with ECA and TCA, respectively. Response was observed in 61.7% (95% CI: 55.3-68) of cases treated with ECA and in 73.1% (95% CI: 67.8-78.5) with TCA (p = .004). The effectiveness of TCA was higher in large and multifocal HSILs. Side effects were common with both treatments, but no serious events were described. Tolerability was good in 77.1% and 80.7% of patients treated with ECA and TCA, respectively. At 24 months, recurrent HSIL were observed in 36.3% (95% CI: 27.3-45) and 28% (95% CI: 20.2-35.8) in the ECA and TCA groups (p = .049). A nadir CD4 cell count ≤200 cells/µl was found to be a risk factor for recurrence (OR: 1.77; 95% CI: 1.12-2.78). CONCLUSIONS: In this study, treatment with TCA showed high effectiveness, low recurrence and good tolerability. Considering the benefits of TCA, it could be considered one of the first-line treatments for anal HSIL.

NKG2C and NKG2A coexpression defines a highly functional antiviral NK population in spontaneous HIV control.

Elite controllers (ECs), a unique group of people with HIV (PWH), exhibit remarkable control of viral replication in the absence of antiretroviral therapy. In this study, we comprehensively characterized the NK cell repertoire in ECs after long-term viral control. Phenotypic profiling of NK cells revealed profound differences compared with other PWH, but marked similarities to uninfected individuals, with a distinctive prevalence of NKG2C+CD57+ memory-like NK cells. Functional analyses indicated that ECs had limited production of functional molecules upon NK stimulation and consequently reduced natural cytotoxicity against non-HIV target cells. Importantly, ECs showed an exceptional ability to kill primary HIV-infected cells by the antibody-dependent cell cytotoxicity adaptive mechanism, which was achieved by a specific memory-like NK population expressing CD16, NKG2A, NKG2C, CD57, and CXCR3. In-depth single-cell RNA-seq unveiled a unique transcriptional signature in these NK cells linked to increased cell metabolism, migration, chemotaxis, effector functions, cytokine secretion, and antiviral response. Our findings underscore a pivotal role of NK cells in the immune control of HIV and identify specific NK cells as emerging targets for immunotherapies.

Developing and validating a clinical risk score to predict losses in the PISCIS cohort of people with HIV.

BACKGROUND: People lost to follow-up (LTFU) from HIV care have an increased risk of worse health. The objective of this study is to create and validate a risk score to predict LTFU among PLWH in Catalonia and the Balearic Islands. METHODS: 6661 PLWH were included. LTFU were those without contact with HIV care for 12 months or more. Logistic regression models were used to assess the role of independent factors on LTFU. The validation included a 10-fold iteration to predict the performance of the regression model and the Area under the ROC Curve (AUC). Regression coefficients were rounded and summed to construct the score. RESULTS: Determinants of LTFU included being younger than 34 years (OR: 1.80, CI, 1.44-2.23), not having been born in Spain (OR: 1.32, 1.11-1.58), men who inject drugs (OR: 2.10, 1.38-3.19), having a detectable viral load (OR: 3.14, 2.47-3.99), and ≤2.5 years since HIV diagnosis (OR: 3.84, 3.10-4.75). The validation of determinants resulted in a mean AUC of 0.69 and the risk-score revealed that 28.8% had a medium and 3.4% a high risk of LTFU respectively. CONCLUSIONS: Findings can be used to prevent LTFU in HIV care.

Prevalence of non-alcoholic fatty liver disease in a multicentre cohort of people living with HIV in Spain.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most important liver comorbidities in people living with HIV (PLWH). Factors that could lead to a higher prevalence of NAFLD or ease the onset of fibrosis are unclear. METHODS: Cohort study of the Spanish HIV Research Network, which comprehends 46 hospitals and more than 15,000 PLWH. Primary objectives were to assess NAFLD prevalence and liver fibrosis according to hepatic steatosis index (HSI) and NAFLD fibrosis score, respectively. Factors associated with both were analysed. RESULTS: A total of 4798 PLWH were included of whom 1461 (30.5%) showed an HSI>36; these patients had higher risk for significant fibrosis (OR 1.91; 95%CI 1.11-3.28). Factors associated with NAFLD were body mass index (OR 2.05; 95%CI 1.94-2.16) and diabetes (OR 4.68; 95%CI 2.17-10.08), while exposure to integrase strand transfer inhibitors showed a lower risk (OR 0.78; 95%CI 0.62-0.97). In patients with HSI>36, being female (OR 7.33; 95%CI 1.34-40), age (OR 1.22; 95%CI 1.11-1.34), body mass index (OR 1.35; 95%CI 1.18-1.54) and exposure to thymidine analogues (OR 75.4, 95%CI 6.9-823.5) were associated with a higher risk of significant fibrosis. However, exposure to non-nucleoside reverse transcriptase inhibitors (OR 0.12, 95%CI 0.02-0.89) and time of exposure to protease inhibitors (OR 0.97, 95%CI 0.95-1) showed a lower risk. CONCLUSION: NAFLD prevalence was high in our cohort. Patients exposed to INSTI showed a lower risk of NAFLD. In patients with hepatic steatosis, exposure to thymidine analogues had 75-fold more risk of significant fibrosis while exposure to NNRTIs reduced this risk.

Impact of very early antiretroviral therapy during acute HIV infection on long-term immunovirological outcomes.

OBJECTIVES: We aimed to determine if starting antiretroviral therapy (ART) in the first 30 days after acquiring HIV infection has an impact on immunovirological response. METHODS: Observational, ambispective study including 147 patients with confirmed acute HIV infection (January/1995-August/2022). ART was defined as very early (≤30 days after the estimated date of infection), early (31-180 days), and late (>180 days). We compared time to viral suppression (viral load [VL] <50 copies/ml) and immune recovery (IR) (CD4+/CD8+ ratio ≥1) according to the timing and type of ART using survival analysis. RESULTS: ART was started in 140 (95.2%) patients. ART was very early in 24 (17.1%), early in 77 (55.0%), and late in 39 (27.9%) cases. Integrase strand transfer inhibitor (INSTI)-based regimens were the most used in both the overall population (65%) and the very early ART group (23/24, 95.8%). Median HIV VL and CD4+/CD8+ ratio pre-ART were higher in the very early ART group (P <0.05). Patients in the very early and early ART groups and treated with INSTI-based regimens achieved IR earlier (P <0.05). Factors associated with faster IR were the CD4+/CD8+ ratio pre-ART (hazard ratio: 9.3, 95% CI: 3.1-27.8, P <0.001) and INSTI-based regimens (hazard ratio: 2.4, 95% CI: 1.3-4.2, P = 0.003). CONCLUSIONS: The strongest predictors of IR in patients who start ART during AHI are the CD4+/CD8+ ratio pre-ART and INSTI-based ART regimens.

Impact of 18F-FDG-PET/CT on the management of Staphylococcus aureus bacteraemia: a retrospective observational study.

OBJECTIVES: To assess the impact of 18F-FDG-PET/CT on the diagnosis and management of patients with Staphylococcus aureus bacteraemia (SAB). METHODS: Post hoc analysis of a prospective cohort of consecutive adult patients diagnosed with SAB (January 2013-December 2017). Patients who underwent 18F-FDG-PET/CT at the discretion of the attending physician were included. Endpoints were the identification of previously unknown infectious foci and changes in clinical management, defined as changes in the duration or class of antibiotic therapy, a surgical procedure on the source of infection or a change in the decision to remove or retain an implantable device. RESULTS: We included 39 patients (median age: 69 years, IQR:60-79). Fifteen (39%) patients did not have an infectious focus identified before 18F-FDG-PET/CT). Thirty new infectious foci were detected in 22/39 (56%) patients. In 11/15 (73%) patients without an identified focus at least one infectious focus was detected by 18F-FDG-PET/CT. In 22/26 (85%) patients with implantable devices, 18F-FDG-PET/CT confirmed or ruled out infection or detected local complications. Out of 13 device infections, 10 were detected by 18F-FDG-PET/CT (7/10 for the first time). In 19/39 (49%) patients 18F-FDG-PET/CT results led to changes in clinical management (15 changes in antibiotic therapy, 2 device removals, 2 surgical procedures, 1 avoidance of a surgical procedure). CONCLUSIONS: 18F-FDG-PET/CT may be a useful asset in the management of selected SAB cases, allowing the identification of previously undetected infectious foci and optimization of therapy, particularly in patients with endovascular devices. Indication should be made on a case-by-case basis.

KLRG1 expression on natural killer cells is associated with HIV persistence, and its targeting promotes the reduction of the viral reservoir.

Human immunodeficiency virus (HIV) infection induces immunological dysfunction, which limits the elimination of HIV-infected cells during treated infection. Identifying and targeting dysfunctional immune cells might help accelerate the purging of the persistent viral reservoir. Here, we show that chronic HIV infection increases natural killer (NK) cell populations expressing the negative immune regulator KLRG1, both in peripheral blood and lymph nodes. Antiretroviral treatment (ART) does not reestablish these functionally impaired NK populations, and the expression of KLRG1 correlates with active HIV transcription. Targeting KLRG1 with specific antibodies significantly restores the capacity of NK cells to kill HIV-infected cells, reactivates latent HIV present in CD4+ T cells co-expressing KLRG1, and reduces the intact HIV genomes in samples from ART-treated individuals. Our data support the potential use of immunotherapy against the KLRG1 receptor to impact the viral reservoir during HIV persistence.

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.

Long-term treatment with nebulized colistin in oncological patients with recurrent respiratory infections.

OBJECTIVES: To assess the efficacy of long-term treatment with nebulized colistin in reducing the number of respiratory infections, emergency consultations and hospitalizations in oncological patients. METHODS: A retrospective, observational, single-centre study including patients with solid or haematologic malignancies, or pulmonary GVHD after HSTC who received treatment with nebulized colistin for at least six-months to prevent recurrent respiratory infections (July 2010 to June 2017). RESULTS: Twelve patients were included (median age: 54.4, range: 23-85), 7 with solid malignancies and 5 with haematologic malignancies (2 with pulmonary GVHD). Pseudomonas aeruginosa was the most frequent microorganism in sputum cultures (11/12 patients), all strains were susceptible to colistin. There was a statistically significant reduction (p=0.01) in respiratory infections in the six-month period after starting colistin (median: 1, range: 0-4) compared to the six-month period before (median: 4, range: 1-8). There was also a reduction in emergency consultations (precolistin: median: 1.50, range: 0-3; postcolistin: median: 0, range: 0-3) and hospitalizations (precolistin: median: 1.50, range: 0-3; postcolistin: median: 0, range: 0-3) due to respiratory infections. No colistin-resistant strains were identified. CONCLUSIONS: Long-term treatment with nebulized colistin may be useful to reduce the number of exacerbations in oncological patients with recurrent respiratory infections.

Identification of HIV-reservoir cells with reduced susceptibility to antibody-dependent immune response.

Human immunodeficiency virus (HIV) establishes a persistent infection in heterogeneous cell reservoirs, which can be maintained by different mechanisms including cellular proliferation, and represent the main obstacle to curing the infection. The expression of the Fcγ receptor CD32 has been identified as a marker of the active cell reservoirs in people on antiretroviral therapy (ART), but if its expression has any role in conferring advantage for viral persistence is unknown. Here, we report that HIV-infected cells expressing CD32 have reduced susceptibility to natural killer (NK) antibody-dependent cell cytotoxicity (ADCC) by a mechanism compatible with the suboptimal binding of HIV-specific antibodies. Infected CD32 cells have increased proliferative capacity in the presence of immune complexes, and are more resistant to strategies directed to potentiate NK function. Remarkably, reactivation of the latent reservoir from antiretroviral-treated people living with HIV increases the pool of infected CD32 cells, which are largely resistant to the ADCC immune mechanism. Thus, we report the existence of reservoir cells that evade part of the NK immune response through the expression of CD32.

Sexual behavior and drug use impact in gay, bisexual, and other men who have sex with men.

BACKGROUND: The emergence of chemsex has raised several concerns about gay, bisexual, and other men who have sex with men's (GBMSM) health. In this study we aim to analyze illicit drugs and chemsex use, sexual behavior and sexually transmitted infections (STI) in GBMSM who attended to a sexual health clinic and to explore any potential association between drug use and STI. METHODS: We conducted an observational study between January and June 2019 among GBMSM population attending to a STI clinic in Barcelona, Spain. An anonymous self-administered questionnaire was given consecutively to all participants older than 18 years who accepted to participate. RESULTS: A total of 514 GBMSM (median age of 34 years-old) were included. The median number of sexual partners in the last year was 20. Seventy-one percent did not use condoms consistently for receptive anal intercourse. Drug abuse prevalence in the preceding year was 64.2%, and 26.5% of the individuals practiced chemsex. Gamma-hydroxibutyrate/gammabutyrolactone, poppers and methamphetamine were the most common drugs in chemsex. Chemsex was associated to group sex (OR 9.8 [95 CI: 4-24]), HIV infection (OR 2.5 [95 CI: 1.1-5.8]), taking pre-exposure prophylaxis (OR 3.2 [95 CI: 1.5-7.1]), developing gonorrhea (OR 3.7 [95 CI: 1.5-8.8]) or syphilis (OR 6.7 [95 CI: 2.4-18.7]). CONCLUSIONS: The prevalence of drug use and chemsex was high among GBMSM in Barcelona. Chemsex was associated with group sex, taking PrEP, and contracting syphilis, gonorrhea, and HIV.

SARS-CoV-2 Vaccination Coverage and Factors Associated with Low Uptake in a Cohort of People Living with HIV.

People living with HIV (PLWH) are prioritised for SARS-CoV-2 vaccination due to their vulnerability to severe COVID-19. Therefore, the epidemiological surveillance of vaccination coverage and the timely identification of suboptimally vaccinated PLWH is vital. We assessed SARS-CoV-2 vaccination coverage and factors associated with under-vaccination among PLWH in Catalonia, Spain. As of 11.12.2021, 9945/14942 PLWH (66.6%) had received ≥1 dose of a SARS-CoV-2 vaccine. Non-Spanish origin (adjusted odds ratio (aOR) 0.64, 95% CI 0.59−0.70), CD4 count of 200−349 cells/µL (aOR 0.74, 95% CI 0.64−0.86) or 350−499 cells/µL (aOR 0.79, 95% CI 0.70−0.88), detectable plasma HIV-RNA (aOR 0.61 95% CI 0.53−0.70), and previous SARS-CoV-2 diagnosis (aOR 0.58 95% CI 0.51−0.65) were associated with under-vaccination. SARS-CoV-2 diagnosis (437 [9.5%] vs. 323 [3.5%], p < 0.001), associated hospitalisations (10 [2.3%] vs. 0 [0%], p < 0.001), intensive care unit admissions (6 [1.4%] vs. 0 [0%], p < 0.001), and deaths (10 [2.3%] vs. 0 [0%], p < 0.001) were higher among unvaccinated PLWH. Vaccination coverage was lower among PLWH with a CD4 count >200 cells/µL, detectable plasma HIV-RNA, previous SARS-CoV-2 diagnosis, and migrants. SARS-CoV-2 diagnosis, associated hospitalisations, and deaths among PLWH were lower among the vaccinated compared with the unvaccinated. SARS-CoV-2 vaccination prioritisation has not completely reached vulnerable PLWH with poorer prognosis. This information can be used to inform public health strategies.

Exploratory study of an oral screening dysplasia program for HIV-infected men who have sex with men.

BACKGROUND: HIV-infected men who have sex with men (MSM) are at high risk to develop human papilloma virus (HPV)-related oropharyngeal cancer. The aim of our study was to assess the usefulness of a pilot oral dysplasia screening program and its correlation with an anal dysplasia screening program. METHODS: This was a prospective study with HIV-infected MSM. Oral and anal screenings were performed based on HPV determination, liquid cytology, direct and microscopy oral examinations, high-resolution anoscopy and biopsies, if necessary. RESULTS: A total of 103 patients were included. The mean age of the patients was 44.6 years, 55.3% were smokers, and 57.3% had a history of previous anal high-grade squamous intraepithelial lesions (HSILs). The prevalence of oral HPV infections was 14% (9% HPV-high risk), the prevalence of abnormal cytology was 25.2%, and in 4.8% of the patients, oral examinations showed suspicious HSILs. Oral microscopy did not detect additional lesions that visual inspection. Five oral biopsies were performed and the results were normal. No risk factors for oral HPV infections were identified. The prevalence of anal HPV infections was 88.3% (76.7% HPV-high risk), 52.9% of the patients had altered cytology, and in 45.6% anoscopy showed changes suggestive of HSILs. Seventy-two anal biopsies were performed, detecting 25 cases of HSILs (24.3%).A poor correlation was observed between oral and anal HPV infections (κ = 0.037). CONCLUSIONS: The prevalence of oral HPV infections, abnormal cytology and lesions in HIV-infected MSM was low, and their correlation with anal HPV-related lesions was slight. These results confirm the current barriers to oral dysplasia screening techniques.

Mortality in Staphylococcus aureus bacteraemia remains high despite adherence to quality indicators: secondary analysis of a prospective cohort study.

OBJECTIVES: To evaluate the association between compliance with previously published quality indicators (QIs) for the management of Staphylococcus aureus bacteraemia (SAB) and 30-day mortality. METHODS: We conducted a post hoc analysis of all adult patients with SAB who were hospitalized at a Spanish university hospital between 2013 and 2018. We evaluated the compliance with 7 QIs of SAB management (i.e., Infectious Diseases consultation, follow-up blood cultures, early source control, echocardiography, early cloxacillin or cefazolin, vancomycin monitoring, and appropriate treatment duration). The QIs compliance rate was considered good if ≥75% of the QIs recommended in each patient were performed. We studied the impact of different risk factors (including QIs compliance) on 30-day all-cause mortality adjusting by multivariable modeling and propensity-matched analysis. RESULTS: We included 441 patients with SAB. The QIs compliance rate was ≥75% in 361 patients (81.9%). A total of 95 patients (21.5%) died within 30 days after the index blood culture. In the multivariable model, the variables associated with 30-day mortality were: age (OR, 1.1; 95% CI, 1.0-1.1), Charlson comorbidity index (OR, 1.2; 95% CI, 1.1-1.4), persistent bacteraemia >72 h (OR, 6.0; 95% CI, 3.2-11.5), infective endocarditis (OR, 2.8; 95% CI, 1.2-6.7), and SAB of unknown source (OR, 3.3; 95% CI, 1.5-7.1). We did not find an association between a global QIs compliance rate of ≥75% or any individual QI with 30-day mortality. CONCLUSIONS: SAB 30-day mortality remains high despite good adherence to previously published QIs for the management of SAB. Future research should focus on additional factors to further improve SAB-related mortality.

Peripheral and lung resident memory T cell responses against SARS-CoV-2.

Resident memory T cells (TRM) positioned within the respiratory tract are probably required to limit SARS-CoV-2 spread and COVID-19. Importantly, TRM are mostly non-recirculating, which reduces the window of opportunity to examine these cells in the blood as they move to the lung parenchyma. Here, we identify circulating virus-specific T cell responses during acute infection with functional, migratory and apoptotic patterns modulated by viral proteins and associated with clinical outcome. Disease severity is associated predominantly with IFNγ and IL-4 responses, increased responses against S peptides and apoptosis, whereas non-hospitalized patients have increased IL-12p70 levels, degranulation in response to N peptides and SARS-CoV-2-specific CCR7+ T cells secreting IL-10. In convalescent patients, lung-TRM are frequently detected even 10 months after initial infection, in which contemporaneous blood does not reflect tissue-resident profiles. Our study highlights a balanced anti-inflammatory antiviral response associated with a better outcome and persisting TRM cells as important for future protection against SARS-CoV-2 infection.

Incidence of malignancy in a Spanish cohort of patients infected by the human immunodeficiency virus. / Incidencia de neoplasias en una cohorte española de pacientes con infección por el virus de la inmunodeficiencia humana.

INTRODUCTION: A higher incidence of malignancies has been described in patients with HIV infection compared to the general population. PATIENTS AND METHODS: Observational retrospective study in patients with HIV infection followed up at the Vall d'Hebron University Hospital (Barcelona, Spain) between 2009 and 2017. The objective of this research was to estimate the incidence of malignancies in HIV patients and their surveillance. Age and sex-adjusted incidence was compared to the incidence calculated by the Spanish Cancer Registry network (REDECAN) in 2015. RESULTS: We included 2,773 patients (41,238 patients-year). Two hundred and eleven malignancies were diagnosed in 182 patients. Non-AIDS defining cancers accounted for 78.2% of the malignancies. The global incidence of cancer was 485 cases per 100,000 person-years. Twenty-year mortality rate was 31.2% in patients with cancer and 7.8% in patients without cancer. In men, adjusted for age, the incidence of malignancies was higher than the incidence in the general population (978.4 vs. 641 cases per 100,000 person-years, P<.001). The most common malignancies in men were lung cancer, Kaposi sarcoma and Hodgkin lymphoma. In women, the incidence of malignancies was not higher than in the general population (340.6 vs. 404.7 cases per 100,000 person-years, P=.27). The most common malignancies among women were lung cancer, head and neck cancer, cervical cancer and Hodgkin's lymphoma. CONCLUSIONS: Men with HIV infection showed a statistically significant higher incidence of malignancies compared to the general Spanish population. Lung cancer was the most common non-AIDS defining cancer.

Impact of 18F-FDG-PET/CT on the management of Staphylococcus aureus bacteraemia: A retrospective observational study / Impacto de la 18F-FDG-PET/TC en el manejo de la bacteriemia por Staphylococcus aureus: resultados de un estudio retrospectivo observacional

Objectives: To assess the impact of 18F-FDG-PET/CT on the diagnosis and management of patients with Staphylococcus aureus bacteraemia (SAB). Methods: Post hoc analysis of a prospective cohort of consecutive adult patients diagnosed with SAB (January 2013–December 2017). Patients who underwent 18F-FDG-PET/CT at the discretion of the attending physician were included. Endpoints were the identification of previously unknown infectious foci and changes in clinical management, defined as changes in the duration or class of antibiotic therapy, a surgical procedure on the source of infection or a change in the decision to remove or retain an implantable device. Results: We included 39 patients (median age: 69 years, IQR: 60–79). Fifteen (39%) patients did not have an infectious focus identified before 18F-FDG-PET/CT. Thirty new infectious foci were detected in 22/39 (56%) patients. In 11/15 (73%) patients without an identified focus at least one infectious focus was detected by 18F-FDG-PET/CT. In 22/26 (85%) patients with implantable devices, 18F-FDG-PET/CT confirmed or ruled out infection or detected local complications. Out of 13 device infections, 10 were detected by 18F-FDG-PET/CT (7/10 for the first time). In 19/39 (49%) patients 18F-FDG-PET/CT results led to changes in clinical management (15 changes in antibiotic therapy, 2 device removals, 2 surgical procedures, 1 avoidance of a surgical procedure). Conclusions: 18F-FDG-PET/CT may be a useful asset in the management of selected SAB cases, allowing the identification of previously undetected infectious foci and optimization of therapy, particularly in patients with endovascular devices. Indication should be made on a case-by-case basis.(AU)

Objetivos: Evaluar el impacto de la 18F-FDG-PET/TC en el diagnóstico y manejo de los pacientes con bacteriemia por Staphylococcus aureus (BSA). Métodos: Análisis post hoc de una cohorte prospectiva de pacientes adultos consecutivos con BSA (enero 2013-diciembre 2017). Se incluyeron aquellos pacientes en los que se realizó una 18F-FDG-PET/TC a criterio del médico tratante. Los criterios de valoración fueron la identificación de nuevos focos infecciosos y los cambios en el manejo clínico (definidos como modificaciones en la duración o clase del tratamiento antibiótico, intervención quirúrgica sobre el foco infeccioso o cambios en la decisión de retirar o mantener un dispositivo implantable). Resultados: Se incluyeron 39 pacientes (edad media: 69 años; RIC: 60-79). En 15 (39%) pacientes no se había identificado un foco infeccioso antes de la 18F-FDG-PET/TC. Se identificaron 30 nuevos focos infecciosos en 22/39 (56%) pacientes. En 11/15 (73%) pacientes sin un foco infeccioso identificado la 18F-FDG-PET/TC detectó al menos un foco infeccioso. En 22/26 (85%) pacientes con dispositivos implantables la 18F-FDG-PET/TC permitió confirmar/descartar infección del dispositivo o detectar complicaciones locales. Diez de 13 infecciones de dispositivos fueron detectadas por 18F-FDG-PET/TC (7/10 desconocidas previamente). En 19/39 (49%) pacientes los hallazgos en la 18F-FDG-PET/TC conllevaron cambios en el manejo clínico (15 modificaciones de tratamiento antibiótico, 2 retiradas de dispositivo, 2 intervenciones quirúrgicas, un procedimiento quirúrgico evitado). Conclusiones: La 18F-FDG-PET/TC puede ser de utilidad en la BSA, ya que permite identificar nuevos focos infecciosos y modificar el manejo clínico, sobre todo en pacientes con dispositivos endovasculares. La indicación ha de individualizarse en cada paciente.(AU)