Prospective study for the early detection of lung carcinoma in patients with HIV infection (GESIDA study 8815).

INTRODUCTION: Lung cancer (LC) screening detects tumors early. The prospective GESIDA 8815 study was designed to assess the usefulness of this strategy in HIV + people (PLHIV) by performing a low-radiation computed tomography (CT) scan. PATIENTS AND METHODS: 371 heavy smokers patients were included (>20 packs/year), >45 years old and with a CD4+ <200 mm3 nadir. One visit and CT scan were performed at baseline and 4 for follow-up time annually. RESULTS: 329 patients underwent the baseline visit and CT (CT0) and 206 completed the study (CT1 = 285; CT2 = 259; CT3 = 232; CT4 = 206). All were receiving ART. A total >8 mm lung nodules were detected, and 9 early-stage PCs were diagnosed (4 on CT1, 2 on CT2, 1 on CT3 and 2 on CT4). There were no differences between those who developed LC and those who did not in sex, age, CD4+ nadir, previous lung disease, family history, or amount of packets/year. At each visit, other pathologies were diagnosed, mainly COPD, calcified coronary artery and residual tuberculosis lesions. At the end of the study, 38 patients quit smoking and 75 reduced their consumption. Two patients died from LC and 16 from other causes (p = 0.025). CONCLUSIONS: The design of the present study did not allow us to define the real usefulness of the strategy. Adherence to the test progressively decreased over time. The diagnosis of other thoracic pathologies is very frequent. Including smokers in an early diagnosis protocol for LC could help to quit smoking.

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.

Neonatal SARS-CoV-2 immunoglobulin G antibodies at delivery and their impact on COVID-19.

OBJECTIVE: To assess neonatal SARS-CoV-2 anti-spike IgG antibody levels after maternal mRNA COVID-19 vaccination and/or infection during pregnancy and evaluate their protective effect. METHODS: Prospective observational study, conducted from January 2021 to December 2022. Infants were tested for anti-spike IgG antibodies at birth and then every 3 months until disappearance of titer. A follow-up was done for SARS-CoV-2 infection up to 12 months. RESULTS: In total, 147 newborns were enrolled with a median (IQR) gestational age of 39.60 weeks (38.3-40.4). Median (IQR) titers in UA/ml at 2 days were higher (P < .001) in newborns of vaccinated 7063.7 (2841.4-14,448.1), than of infected mothers 372.7 (158.00-884.90). Titers dropped significantly during the follow-up but 50% still had a detectable titer at 6 months. A high antibody titer at 2 days led to a longer persistence (HR 0.89, IC 95% 0.83-0.96, P = .004). In total, 36 infants were infected during the first months of life coinciding with the Omicron variant. Fifty percent had detectable antibodies during the infection period. Relationship between high IgG titers and month of infection was inverse (RHO - 0.52, P = .009). CONCLUSION: Though a high antibody titer at birth led to longer persistence, no protective effect against infection was found. As newborns are a high risk group for COVID-19, avoiding transmission during the first year of life is important.

Disparities in Coronavirus Disease 2019 Clinical Outcomes and Vaccination Coverage Among Migrants With Human Immunodeficiency Virus in the PISCIS Cohort: A Population-Based Propensity Score-Matched Analysis.

Background: Coronavirus disease 2019 (COVID-19) disproportionately affects migrants and ethnic minorities, including those with human immunodeficiency virus (HIV). Comprehensive studies are needed to understand the impact and risk factors. Methods: Using data from the PISCIS cohort of people with HIV (PWH) in Catalonia, Spain, we investigated COVID-19 outcomes and vaccination coverage. Among 10 640 PWH we compared migrants and non-migrants assessing rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, diagnosis, and associated clinical outcomes through propensity score matching and multivariable Cox regression. Results: The cohort (mean age, 43 years; 83.5% male) included 57.4% (3053) Latin American migrants. Migrants with HIV (MWH) had fewer SARS-CoV-2 tests (67.8% vs 72.1%, P < .0001) but similar COVID-19 diagnoses (29.2% vs 29.4%, P = .847) compared to Spanish natives. Migrants had lower complete vaccination (78.9% vs 85.1%, P < .0001) and booster doses (63.0% vs 65.5%, P = .027). COVID-19 hospitalizations (8.1% vs 5.1%, P < .0001) and intensive care unit (ICU) admissions (2.9% vs 1.2%, P < .0001) were higher among migrants, with similar hospitalization duration (5.5 vs 4.0 days, P = .098) and mortality (3 [0.2%] vs 6 [0.4%], P = .510). Age ≥40 years, CD4 counts <200 cells/µL, ≥2 comorbidities, and incomplete/nonreception of the SARS-CoV-2 vaccine increased the risk of severe COVID-19 among migrants. Conclusions: MWH had lower rates of SARS-CoV-2 testing and vaccination coverage, although the rates of COVID-19 diagnosis were similar between migrants and non-migrants. Rates of COVID-19-associated hospitalizations and ICU admissions were higher among migrants in comparison with non-migrants, with similar hospitalization duration and mortality. These findings can inform policies to address disparities in future pandemic responses for MWH.

Time from symptoms onset to remdesivir is associated with the risk of ICU admission: a multicentric analyses.

BACKGROUND: Shorter duration of symptoms before remdesivir has been associated with better outcomes. Our goal was to evaluate variables associated with the need of ICU admission in a cohort of hospitalized patients for COVID-19 under remdesivir including the period from symptoms onset to remdesivir. METHODS: We conducted a retrospective multicentric study analysing all patients admitted with COVID-19 in 9 Spanish hospitals who received treatment with remdesivir in October 2020. The main outcome was the need of ICU admission after 24 h of the first dose of remdesivir. RESULTS: In our cohort of 497 patients, the median of days from symptom onset to remdesivir was 5 days, and 70 of them (14.1%) were later admitted into ICU. The clinical outcomes associated with ICU admission were days from symptoms onset (5 vs. 6; p = 0.023), clinical signs of severe disease (respiratory rate, neutrophil count, ferritin levels and very-high mortality rate in SEIMC-Score) and the use of corticosteroids and anti-inflammatory drugs before ICU. The only variable significatively associated with risk reduction in the Cox-regression analyses was ≤ 5 days from symptoms onset to RDV (HR: 0.54, CI95%: 0.31-0.92; p = 0.024). CONCLUSION: For patients admitted to the hospital with COVID-19, the prescription of remdesivir within 5 days from symptoms onset diminishes the need of ICU admission.

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.

Spread of SARS-CoV-2 in hospital areas.

We performed a systematic sampling and analysis of airborne SARS-CoV-2 RNA in different hospital areas to assess viral spread. Systematic air filtration was performed in rooms with COVID-19 infected patients, in corridors adjacent to these rooms, to rooms of intensive care units, and to rooms with infected and uninfected patients, and in open spaces. RNA was extracted from the filters and real-time reverse transcription polymerase chain reaction was performed using the LightMix Modular SARS-CoV-2 E-gene. The highest occurrence of RNA was found in the rooms with COVID-19 patients (mean 2600 c/m3) and the adjacent corridor (mean 4000 c/m3) which was statistically significant more exposed (p < 0.01). This difference was related to the ventilation systems. As is commonly found in many hospitals, each of the rooms had an individual air inlet and outlet, while in the corridors these devices were located at the distance of every four rooms. There was a significant transfer of viruses from the COVID-19 patients' rooms to the corridors. The airborne SARS-CoV-2 RNA in the corridors of ICUs with COVID-19 patients or care rooms of uninfected patients were ten times lower, averages 190 c/m3 and 180 c/m3, respectively, without presenting significant differences. In all COVID-19 ICU rooms, patients were intubated and connected to respirators that filtered all exhaled air and prevented virus release, resulting in significantly lower viral concentrations in adjacent corridors. The results show that the greatest risk of nosocomial infection may also occur in hospital areas not directly exposed to the exhaled breath of infected patients. Hospitals should evaluate the ventilation systems of all units to minimize possible contagion and, most importantly, direct monitoring of SARS-CoV-2 in the air should be carried out to prevent unexpected viral exposures.

Predictive Immunological, Virological, and Routine Laboratory Markers for Critical COVID-19 on Admission.

BACKGROUND: Early identification of COVID-19 patients at risk of critical illness is a challenging endeavor for clinicians. We aimed to establish immunological, virological, and routine laboratory markers, which, in combination with clinical information, may allow identifying such patients. METHODS: Blood tests to measure neutrophil/lymphocyte ratio (NLR) and levels of ferritin, CRP, D-dimer, complement components (C3 and C4), cytokines, and lymphocyte subsets, as well as SARS-Cov-2 RT-PCR tests, were performed in COVID-19-confirmed cases within 48 hours of admission. RT-PCR cycle threshold (Ct) values from oropharyngeal or nasopharyngeal swabs were determined on the day of admission. Symptom severity was categorized as mild (grade 1), severe (grade 2), or critical (grade 3). RESULTS: Of 120 patients who were included, 49 had mild, 32 severe, and 39 critical COVID-19. Levels of ferritin >370 ng/mL (OR 16.4, 95% CI 5.3-50.8), D-dimer >440 ng/mL (OR 5.45, 95% CI 2.36-12.61), CRP >7.65 mg/dL (OR 11.54, 95% CI 4.3-30.8), NLR >3.77 (OR 13.4, 95% CI 4.3-41.1), IL-6 >142.5 pg/mL (OR 8.76, 95% CI 3.56-21.54), IL-10 >10.8 pg/mL (OR 16.45, 95% CI 5.32-50.81), sIL-2rα (sCD25) >804.5 pg/mL (OR 14.06, 95% CI 4.56-43.28), IL-1Ra >88.4 pg/mL (OR 4.54, 95% CI 2.03-10.17), and IL-18 >144 pg/mL (OR 17.85, 95% CI 6.54-48.78) were associated with critical COVID-19 in the univariate age-adjusted analysis. This association was confirmed in the multivariate age-adjusted analysis only for ferritin, CRP, NLR, IL-10, sIL-2rα, and IL-18. T, B, and NK cells were significantly decreased in critical patients. SARS-CoV-2 was not detected in blood except in 3 patients who had indeterminate results. RT-PCR Ct values from oropharyngeal or nasopharyngeal swabs on admission were not related to symptom severity. CONCLUSION: Ferritin, D-dimer, CRP, NLR, cytokine (IL-18 and IL-10), and cytokine receptor (IL-6, IL1-Ra, and sCD25) test results combined with clinical data can contribute to the early identification of critical COVID-19 patients.

Effects of first-line antiretroviral therapy on the CD4/CD8 ratio and CD8 cell counts in CoRIS: a prospective multicentre cohort study.

BACKGROUND: A low CD4/CD8 ratio during antiretroviral therapy (ART) identifies people with heightened immunosenescence and increased risk of mortality. We aimed to assess the effects of integrase strand transfer inhibitor (INSTI)-based, protease inhibitor-based, or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART on long-term CD4/CD8 ratio recovery. METHODS: This prospective cohort study included 13 026 individuals with HIV registered in the Spanish HIV Research Network (CoRIS) cohort recruited from 45 Spanish hospitals. We included HIV-positive people who started triple ART (two nucleoside reverse transcriptase inhibitors [NRTI] with a NNRTI, protease inhibitor, or INSTI) and had HIV RNA suppression within 48 weeks. We used piecewise linear mixed models adjusted for potential confounders to compare longitudinal changes in the CD4/CD8 ratio between people receiving three different types of ART. We used Cox proportional-hazard models to compare the times to CD4/CD8 normalisation between the treatment groups, using cutoff ratios of 0·4, 1·0, and 1·5. FINDINGS: 6804 individuals contributing 37 149 persons-years and 37 680 observations were analysed; median follow-up was 49 months (IQR 22-89). INSTI-based ART was associated with greater CD4/CD8 gain (change per year compared with INSTI was coefficient -0·07 [95% CI -0·08 to -0·06] for NNRTI and was -0·08 [-0·09 to -0·08] for protease inhibitors). Differences were observed from the first year of therapy and were driven by changes in both CD4 and CD8 cell counts. Subanalyses at different time periods suggested that these differences were driven by changes during the first year of ART without significant differences in the adjusted CD4/CD8 ratio trajectories after the second year of ART (change per year compared with INSTI was coefficient -0·03 [95% CI -0·05 to -0·13] for NNRTI and was -0·06 [95% CI -0·08 to -0·04] for protease inhibitors). Although no differences in the time until CD4/CD8 normalisation at a cutoff ratio of no less than 0·4 were reported between any of the groups, compared with the INSTI group, both the NNRTI and protease inhibitor groups showed lower rates of normalisation at cutoff ratios of 1·0 or more (adjusted hazard ratio 0·80 [95% CI 0·72-0·89] for the NNRTI group and 0·79 [0·69-0·89] for the protease inhibitor group), and 1·5 or more (0·79 [0·65-0·95] for the NNRTI group and 0·78 [0·64-0·97] for the protease inhibitor group). No differences were found between the different integrases in the time until CD4/CD8 normalisation. Subanalyses adjusted for the backbone NRTIs and allowing observations after virological failure yielded similar results. INTERPRETATION: This study provides new evidence that reinforces the positioning of INSTI-based therapies as a first choice and underlines the importance of analysing the effects of therapeutic interventions on biomarkers linked with morbidity and mortality beyond the plasma HIV RNA and the CD4 cell counts. FUNDING: Spanish AIDS Research Network (Instituto de Salud Carlos III), European Development Regional Fund "A way to achieve Europe".

Increased rate of FEV1 decline in HIV patients despite effective treatment with HAART.

INTRODUCTION: Previous studies have reported that the rate of FEV1 decline over time is increased in HIV patients but the mechanisms underlying this observation are unclear. Since current HIV treatment with Highly Active Antiretroviral Therapy (HAART) results in very good immune-viral control, we hypothesized that HAART should normalize the elevated rate of FEV1 decline previously reported in HIV patients if it was somehow related to the immune alterations caused by HIV, particularly in never smokers or quitters, since smoking is a well established risk factor for accelerated FEV1 decline in the general population. METHODS: We explored this hypothesis in a prospectively recruited cohort of 188 HIV (smoker and non-smoker) patients treated with HAART in Palma de Mallorca (Spain) and followed-up for 6 years. The cross-sectional characteristics of this cohort have been published elsewhere. RESULTS: We found that: (1) HAART resulted in good immune-viral control; (2) the rate of FEV1 decline remained abnormally elevated, even in non-smokers and quitters; and, (3) alcohol abuse during follow-up was related to FEV1 decline in these patients. DISCUSSION: Despite adequate immune-viral control by HAART, lung function decline remains increased in most HIV patients, even in non-smokers and quitters. Alcohol abuse is a preventable risk factor to decrease the accelerated FEV1 decline in this population.

Interatrial blocks prevalence and risk factors for human immunodeficiency virus-infected persons.

BACKGROUND: Interatrial blocks are considered a new important risk factor for atrial fibrillation and cerebrovascular events. Their prevalence and clinical implications have been reported in general population and several subgroups of patients but no data from HIV-infected populations, with a non-negligible prevalence of atrial fibrillation, has been previously reported. METHODS: We conducted a cross-sectional study in a previously enrolled cohort of randomly selected middle-aged HIV-infected patients who attended our hospital and were clinically stable. Patients underwent both a 12-lead rest electrocardiogram and clinical questionnaires while epidemiological, clinical and HIV-related variables were obtained from electronic medical records and interviews with the patients. Electrocardiograms were then analyzed and codified using a standardized form by two trained members of the research team who were blinded to clinical variables. RESULTS: We obtained electrocardiograms from 204 patients with a mean age of 55.22 years, 39 patients (19.12%) presented an interatrial block, 9 (4.41%) advanced and 30 (14.71%) partial. Patients with interatrial block had a lower nadir lymphocyte CD4 count (124 vs 198 cells, p = 0.02) while advanced interatrial blocks were associated to older age (62.16 vs. 54.95 years, p = 0.046) and hypertension (77.8% vs. 32.3%, p = 0.009). We did not find differences regarding baseline CD4 lymphocyte count or CD4/CD8 lymphocyte ratio. Clinical variables and functional capacity among patients with or without interatrial block were similar. CONCLUSIONS: In a cohort of clinically stable HIV infected patients the prevalence of interatrial blocks, specially advanced, is high and associated to previously known factors (age, hypertension) and novel ones (nadir CD4 lymphocyte count).

Calvarial tuberculosis: an unusual presentation of disseminated tuberculosis.

A 30-year-old man, without previous medical record, was admitted to our centre due to persistent hacking cough for the previous 2 months, accompanied by nocturnal sweating, unquantified weight loss and low-grade fever. The patient was finally diagnosed of pulmonary tuberculosis (TB). During admission, a right forehead swelling was detected, painful to palpation, fluctuating and not attached to the skin, without cutaneous alterations or neurological impairment. Surgical debridement was performed and intraoperative cultures were positive for mycobacteria TB. The patient completed 9 months of antituberculous therapy and fully recovered.