Assessing ChatGPT's Potential in HIV Prevention Communication: A Comprehensive Evaluation of Accuracy, Completeness, and Inclusivity.

With the advancement of artificial intelligence(AI), platforms like ChatGPT have gained traction in different fields, including Medicine. This study aims to evaluate the potential of ChatGPT in addressing questions related to HIV prevention and to assess its accuracy, completeness, and inclusivity. A team consisting of 15 physicians, six members from HIV communities, and three experts in gender and queer studies designed an assessment of ChatGPT. Queries were categorized into five thematic groups: general HIV information, behaviors increasing HIV acquisition risk, HIV and pregnancy, HIV testing, and the prophylaxis use. A team of medical doctors was in charge of developing questions to be submitted to ChatGPT. The other members critically assessed the generated responses regarding level of expertise, accuracy, completeness, and inclusivity. The median accuracy score was 5.5 out of 6, with 88.4% of responses achieving a score ≥ 5. Completeness had a median of 3 out of 3, while the median for inclusivity was 2 out of 3. Some thematic groups, like behaviors associated with HIV transmission and prophylaxis, exhibited higher accuracy, indicating variable performance across different topics. Issues of inclusivity were identified, notably the use of outdated terms and a lack of representation for some communities. ChatGPT demonstrates significant potential in providing accurate information on HIV-related topics. However, while responses were often scientifically accurate, they sometimes lacked the socio-political context and inclusivity essential for effective health communication. This underlines the importance of aligning AI-driven platforms with contemporary health communication strategies and ensuring the balance of accuracy and inclusivity.

Occupational Risk for Coronary Artery Disease in Shift Workers - A Systematic Review.

BACKGROUND: Coronary artery disease (CAD) prevention in shift workers (SWs) poses a significant challenge worldwide, as CAD remains a major cause of mortality and disability. In the past, SWs were found at higher risk of CAD than non-s SWs. Nevertheless, the pathogenic mechanism between shift work and CAD to date is unclear. This systematic review aims to enhance understanding of the risk of CAD occurrence in SWs. METHODS: A systematic literature review was conducted from January 2013 to December 2023. MEDLINE/Pubmed databases were used initially, and additional relevant studies were searched from references. Shift work was defined as any schedule outside traditional shifts, including the night shift. RESULTS: Fifteen pertinent papers were categorized into risk assessment or risk management. Findings demonstrated an increased risk of CAD among SWs compared to non-SWs, with an increased CAD risk observed for both shift work and night shift work. DISCUSSION: Duration-response associations indicate that greater shift exposure is linked to higher CAD risk. SWs incur an increased risk of CAD through the atherosclerotic process. As shift work duration increases as the risk of atherosclerosis is higher, workers demonstrate a higher prevalence and severity of coronary artery plaques. CONCLUSIONS: The evidence-based results underscore the increased risk of CAD in SWs and are sufficient for proposing guidelines aimed at reducing the risk of CAD in SWs and at managing people with CAD in return to work characterized by disrupted circadian rhythms.

Resting-state EEG rhythms are abnormal in post COVID-19 patients with brain fog without cognitive and affective disorders.

OBJECTIVES: Several persons experiencing post-covid-19 (post-COVID) with "brain fog" (e.g., fatigue, cognitive and psychiatric disorders, etc.) show abnormal resting-state electroencephalographic (rsEEG) rhythms reflecting a vigilance dysfunction. Here, we tested the hypothesis that in those post-COVID persons, abnormal rsEEG rhythms may occur even when cognitive and psychiatric disorders are absent. METHODS: The experiments were performed on post-COVID participants about one year after hospitalization for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Inclusion criteria included a "brain fog" claim, no pre-infection, and actual organic chronic disease. Matched controls (no COVID) were also enrolled. All participants underwent clinical/neuropsychological assessment (including fatigue assessment) and rsEEG recordings. The eLORETA freeware estimated regional rsEEG cortical sources at individual delta (<4 Hz), theta (4-7 Hz), and alpha (8-13 Hz) bands. Beta (14-30 Hz) and gamma (30-40 Hz) bands were pre-fixed. RESULTS: More than 90% of all post-COVID participants showed no cognitive or psychiatric disorders, and 75% showed ≥ 2 fatigue symptoms. The post-COVID group globally presented lower posterior rsEEG alpha source activities than the Control group. This effect was more significant in the long COVID-19 patients with ≥ 2 fatigue symptoms. CONCLUSIONS: In post-COVID patients with no chronic diseases and cognitive/psychiatric disorders, "brain fog" can be associated with abnormal posterior rsEEG alpha rhythms and subjective fatigue. SIGNIFICANCE: These abnormalities may be related to vigilance and allostatic dysfunctions.

The Epidemiology of Anal Human Papillomavirus (HPV) in HIV-Positive and HIV-Negative Women and Men: A Ten-Year Retrospective Observational Study in Rome (Italy).

Human papillomaviruses (HPVs) commonly infect the anogenital mucosa; most infections are transient, but a fraction of those caused by high-risk (HR) types persist and may lead to anogenital cancer. The epidemiology of HPV genotypes in anal infections in groups at different risk for anal cancer has not been well described in Italy. This retrospective study reports the results of HPV DNA testing and complete genotyping performed on anal swabs from 691 female and male patients attending proctology clinics in Rome during 2012-2021; one-third had repeated testing. Cumulative HPV positivity in 1212 anal swabs was approximately 60%, was not age related, and showed an increasing trend over the study period. HPV rates differed significantly by sex and HIV status: HIV-negative women had the lowest (43.6%) and HIV-positive men the highest (83.5%) HPV prevalence. HIV-positive men had more oncogenic HPV genotypes detected, more multiple infections, and the highest frequency of persistent infections. Two-thirds of all infections were vaccine-preventable. This study found that anal HPV infection rates are still elevated and even increasing in groups at low and high risk of developing anal cancer. Prevention programs need to be improved to reduce rates of anal infection in young women and men.

Knowledge of Sexually Transmitted Infections and HIV among People Living with HIV: Should We Be Concerned?

Poor knowledge of sexually transmitted infections (STIs) and HIV among people with HIV (PLHIV) could worsen life quality. We aimed to investigate their STI and HIV knowledge, disclosure and undetectable = untransmittable (U=U). We proposed an anonymous questionnaire regarding STI and HIV to PLHIV attending ten Italian outpatient infectious diseases clinics. Moreover, disclosure and U=U were investigated. The calculated sample size was 178 people. Considering a missing response of 10%, the final sample size was 196. We enrolled 200 PLHIV (73.5% males), with a median age of 52.5 (IQR 41-59) years. The mean score was 7.61 ± 1.22 with no difference by gender, education, and employment. Significant statistical difference was observed by sexual orientation; bisexuals and those who preferred not to answer had a lower score than heterosexuals and MSM (p = 0.0032). PLHIV showed poor knowledge about HIV transmission (25% appropriately answered). Nearly 30% responded that virologically suppressed PLHIV could transmit the infection. Finally, 137 (68.5%) and 158 (79.0%) disclosed to the general practitioner and family and friends, respectively. Nearly 52.0% knew the meaning of U=U, and 83.6% highlighted its positive rebound. In conclusion, important knowledge gaps are present among PLHIV regarding U=U, and its implications are little-known. Improving PLHIVs' awareness will undermine self-stigma and enhance life quality.

Optimizing the antiretroviral treatment focusing on long-term effectiveness and a person-centered approach. Consensus Guidance Using a Delphi Process.

Definitive data on the long-term success of the latest antiretroviral therapy (ART) strategies are still lacking. A panel of infectious diseases specialists was convened to develop a consensus on how to tailor and follow ART over time. Panelists used a Delphi technique to develop a list of statements describing preferred management approaches for ART and patient monitoring and quality of life evaluation. Ninety infectious diseases specialists from several Infectious Diseases Centers in Italy participated in the consensus process. A consensus was reached on virological and immunological parameters to use to monitor long-term efficacy of antiretroviral treatment, while there was no consensus on the use of specific inflammation and immune-activation markers in clinical routine. The panel agreed on the need for an antiretroviral treatment with the lowest impact on bone, kidney and cardiovascular toxicity and on the utility of quality-of-life monitoring during the standard follow up of people living with HIV. The consensus statements developed by a panel of infectious diseases specialists may provide guidance to practitioners for a person-centered approach aimed at obtaining long-term virological and clinical success for people living with HIV.

Right to Occupational Safety: Prevalence of Latent Tuberculosis Infection in Healthcare Workers. A 1-Year Retrospective Survey Carried out at Hospital of Lecce (Italy).

BACKGROUND: Prevention of latent tuberculosis infection (LTBI) in healthcare workers (HCWs) to ensure the "Right to Occupational Safety" is a special challenge globally, as HCWs have a higher risk of acquiring the infection in hospital settings because of frequent close exposure to patients suffering from tuberculosis (TB). METHODS: Aretrospective study was performed with the aim of assessing the prevalence of LTBI related to demographical and occupational risk factors among HCWs employed in a large hospital in Italy. The study involved 1461 HCWs screened for LTBI by Mantoux tuberculin skin test (TST) and then confirmed with Interferon Gamma Release Assay (IGRA) test in case of positivity. Immunosuppressed and BGC-vaccinated workers were tested directly with IGRA. RESULTS: LTBI was diagnosed in 4.1% of the HCWs and the prevalence resulted lower than other studies conducted in low TB incidence countries. The variables significantly linked with higher frequency of the infection were: age ≥40 years (OR = 3.14; 95% CI: 1.13-8.74; p < 0.05), length of service ≥15 years (OR = 4.11; 95% CI: 1.48-11.43; p < 0.05) and not being trained on TB prevention (OR = 3.46; 95% CI: 1.85-6.46; p < 0.05). Not trained HCWs presented a higher risk of LTBI also after adjustment for age and length of service, compared to trained HCWs. CONCLUSIONS: screening of HCWs for LTBI should be always considered in routinely occupational surveillance in order to early diagnose the infection and prevent its progression. Safety policies in hospital settings centered on workers' training on TB prevention is crucial to minimize LTBI occurrence in HCWs.

Differential expression of Type I interferon and inflammatory genes in SARS-CoV-2-infected patients treated with monoclonal antibodies.

INTRODUCTION: Considering the reported efficacy of monoclonal antibodies (mAbs) directed against the Spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in reducing disease severity, the aim of this study was to investigate the innate immune response before and after mAbs treatment in 72 vaccinated and 31 unvaccinated SARS-CoV-2 patients. METHODS: The mRNA levels of IFN-I, IFN-related genes and cytokines were evaluated using RT/real-time quantitative PCR. RESULTS: Vaccinated patients showed increased rate of negative SARS-CoV-2 PCR tests on nasopharyngeal swab compared with unvaccinated ones after mAbs treatment (p = .002). Unvaccinated patients had lower IFN-α/ω and higher IFN-related genes (IFNAR1, IFNAR2, IRF9, ISG15, ISG56 and IFI27) and cytokines (IL-6, IL-10 and TGF-ß) mRNA levels compared to vaccinated individuals before mAbs (p < .05 for all genes). Increased IFN-α/ω, IFNAR1, IFNAR2 and IRF9 levels were observed in unvaccinated patients after mAbs treatment, while the mRNA expression ISGs and IL-10 were reduced in all patients. CONCLUSION: These data suggest that anti-S vaccinated patients have increased levels of innate immune genes compared to unvaccinated ones. Also, gene expression changes in IFN genes after mAbs administration are different according to the vaccination status of patients.

Efficacy and tolerability of dolutegravir/lamivudine versus dolutegravir/rilpivirine in switching from a three-drug regimen based on nonnucleoside reverse transcriptase inhibitors: A retrospective cohort study.

Real-life comparisons of dolutegravir/rilpivirine (DTG/RPV) and DTG/lamivudine (3TC) regimens in people living with human immunodeficiency virus (PLWHIV) who switched from a standard three-drug regimen based on nonnucleoside reverse transcriptase inhibitors (NNRTIs) are missing. This study aimed to compare DTG/3TC and DTG/RPV in virologically suppressed patients (HIV-RNA < 50 copies/mL) coming from any NNRTI-based regimen in terms of discontinuation due to virologic failure (VF) discontinuation rates due to all causes, and adverse events. As a secondary outcome, we evaluated the difference in creatinine, total cholesterol, CD4, and triglycerides from baseline to weeks 48 after the switch. Of the 415 PLWHs included in the study, 278 (66.9%) switched to DTG/3TC, and 137 (33.1%) switched to DTG/RPV. Overall, 48 PLWHs (11.6%) discontinued the treatment:38 with DTG/3TC and 10 with DTG/RPV with similar discontinuation rates: 5.01 × 100 py (95% confidence interval [CI] 3.64-6.94) and 4.66 × 100 py (95% CI 2.51-8.67), respectively. The most common reason for discontinuation was toxicity (26 patients, 22/278 [7.9%] in the DTG/3TC group and 4/137 [2.9%] in the DTG/RPV group), mainly neurologic toxicity (never above grade 2). We found no differences in discontinuation rates due to treatment adverse events. Two study participants experienced virological failure in the DTG/3TC arm. We observed no significant difference in CD4 cell counts, lipid parameters, or renal function between the two groups at 48 weeks. This study demonstrated that, in clinical practice, a two-drug regimen with DTG/3TC or DTG/RPV is characterized by a low discontinuation rate and VF in virologically suppressed PLWHs switched from an NNRTI-based three antiretroviral drugs regimen.

Reduced Reliability of Procalcitonin (PCT) as a Biomarker of Bacterial Superinfection: Concerns about PCT-Driven Antibiotic Stewardship in Critically Ill COVID-19 Patients-Results from a Retrospective Observational Study in Intensive Care Units.

BACKGROUND: The aim of this study was to assess whether procalcitonin levels is a diagnostic tool capable of accurately identifying sepsis and ventilator-associated pneumonia (VAP) even in critically ill COVID-19 patients. METHODS: In this retrospective, observational study, all critically ill COVID-19 patients who survived for ≥2 days in a single university hospital and had at least one serum procalcitonin (PCT) value and associated blood culture and/or culture from a lower respiratory tract specimen available were eligible for the study. RESULTS: Over the research period, 184 patients were recruited; 67 VAP/BSI occurred, with an incidence rate of 21.82 episodes of VAP/BSI (95% CI: 17.18-27.73) per 1000 patient-days among patients who were included. At the time of a positive microbiological culture, an average PCT level of 1.25-3.2 ng/mL was found. Moreover, also in subjects without positive cultures, PCT was altered in 21.7% of determinations, with an average value of 1.04-5.5 ng/mL. Both PCT and PCT-72 h were not linked to a diagnosis of VAP/BSI in COVID-19 patients, according to the multivariable GEE models (aOR 1.13, 95% CI 0.51-2.52 for PCT; aOR 1.32, 95% CI 0.66-2.64 for PCT-72 h). CONCLUSION: Elevated PCT levels might not always indicate bacterial superinfections or coinfections in a severe COVID-19 setting.

Parietal resting-state EEG alpha source connectivity is associated with subcortical white matter lesions in HIV-positive people.

OBJECTIVE: Parietal resting-state electroencephalographic (rsEEG) alpha (8-10 Hz) source connectivity is abnormal in HIV-positive persons. Here we tested whether this abnormality may be associated with subcortical white matter vascular lesions in the cerebral hemispheres. METHODS: Clinical, rsEEG, and magnetic resonance imaging (MRI) datasets in 38 HIV-positive persons and clinical and rsEEG datasets in 13 healthy controls were analyzed. Radiologists visually evaluated the subcortical white matter hyperintensities from T2-weighted FLAIR MRIs (i.e., Fazekas scale). In parallel, neurophysiologists estimated the eLORETA rsEEG source lagged linear connectivity from parietal cortical regions of interest. RESULTS: Compared to the HIV participants with no/negligible subcortical white matter hyperintensities, the HIV participants with mild/moderate subcortical white matter hyperintensities showed lower parietal interhemispheric rsEEG alpha lagged linear connectivity. This effect was also observed in HIV-positive persons with unimpaired cognition. This rsEEG marker allowed good discrimination (area under the receiver operating characteristic curve > 0.80) between the HIV-positive individuals with different amounts of subcortical white matter hyperintensities. CONCLUSIONS: The parietal rsEEG alpha source connectivity is associated with subcortical white matter vascular lesions in HIV-positive persons, even without neurocognitive disorders. SIGNIFICANCE: Those MRI-rsEEG markers may be used to screen HIV-positive persons at risk of neurocognitive disorders.

Pillars of long-term antiretroviral therapy success.

BACKGROUND: Meeting the challenge of antiretroviral therapy (ART) whose efficacy can last a lifetime requires continuous updating of the virological, pharmacological, and quality of life outcomes to be pursued and a continuous review of literature data on the efficacy and tolerability of new drugs and therapeutic strategies. METHODS: With the aim of identifying open questions and answers about the current controversies in modern ART, we adapted the Design Thinking methodology to the needs of the design phase of a scientific article, involving a team of experts in HIV care. RESULTS: Five main pillars of treatment success were discussed: sustained virologic suppression over time; immunological recovery; pharmacological attributes; long-term tolerability and safety of ART; and people's satisfaction and quality of life. The definition of the outcomes to be achieved in each thematic area and the tools to achieve them were reviewed and discussed. CONCLUSIONS: Long-term treatment success should be intended as a combination of HIV-RNA suppression, immune recovery, and high quality of life. To achieve this, the regimen should be well-tolerated, with high potency, genetic barrier, and forgiveness, and should be tailored by a person-centered perspective, based on individual needs, preferences, and therapeutic history.

MicroRNA Expression Levels in Peripheral Blood Mononuclear Cells from Human Immunodeficiency Virus Type 1 Positive Individuals and Relationship with Different Levels of Viral Suppression.

The persistence of low human immunodeficiency virus type 1 (HIV-1) replication in individuals undergoing antiretroviral therapy (ART) still threatens their health. Previous findings have shown that microRNAs (miRNAs) could interfere with several steps of the viral life cycle. Herein, we set out to investigate the expression of miR-150, miR-223, miR-382, miR-324-5p, miR-33a-5p, miR-34a, and miR-132 in the whole peripheral blood mononuclear cell (PBMC) population from people living with HIV-1 showing different levels of viral suppression. Levels of PBMC-associated miRNAs were analyzed in 30 individuals with undetectable viremia (target not detected) and 30 individuals with detectable low-level viremia (1-200 copies/mL). In addition, 30 samples from treatment-naive (NAIVE) individuals were investigated. Results were compared to a control group of 28 HIV-negative donors. All miRNAs analyzed were strongly downregulated in the NAIVE population, either compared to the treated group or to controls. Stratification of ART-treated donors according to the therapeutic regimen showed the downregulation of miR-33a-5p in subjects treated with non-nucleoside reverse transcriptase inhibitors compared with those treated with protease inhibitors. Collectively, the present study shows that uncontrolled viral replication leads to profound miRNA deregulation while treated individuals, irrespective of the degree of viral suppression, and even the types of antiviral drugs seem to be specifically associated with miRNA expression profiles. These evidences suggest that virological suppression could be favored by miRNA modulation.

Immune Reconstitution and Safe Metabolic Profile after the Switch to Bictegravir/Emtricitabine/Tenofovir Alafenamide Fumarate among Virologically Controlled PLWH: A 96 Week Update from the BICTEL Cohort.

BACKGROUND: Bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) is a recommended once-daily single-tablet regimen for the treatment of people living with HIV (PLWH). We aimed to assess efficacy, safety, and tolerability of BIC/FTC/TAF among PLWH, with a specific focus on people older than 55 years. METHODS: We recruited an observational retrospective real-life cohort, including all PLWH who underwent a therapeutic switch to BIC/FTC/TAF, independently from the previous treatment regimen (the BICTEL cohort). Longitudinal nonparametric analyses and linear models were built. RESULTS: After 96 weeks of follow-up, 164 PLWH were included, with 106 older than 55. Both the intention-to-treat and the per-protocol analysis showed low rates of virologic failure, independent of the pre-switch anchor drug. At week 96, a significant increase in CD4+ T cell count and in CD4+/CD8+ ratio was observed, inversely correlated with baseline immune status. Fasting serum lipid profile, total body weight, BMI, and hepatic function were not affected by the switch, without new onset of metabolic syndrome or weight gain. Compared to baseline, we observed a renal function worsening which is worthy of further follow-up. CONCLUSION: BIC/FTC/TAF is an effective, safe, and well-tolerated switching strategy for PLWH, especially among those older than 55.

Chronic Suppressive Antibiotic Treatment for Staphylococcal Bone and Joint Implant-Related Infections.

Prosthetic joint infection (PJI) and fracture-related infection (FRI) are difficult-to-treat conditions in patients with severe comorbidity or significant surgical risk. In cases not eligible for standard strategy, debridement procedures with the retention of prosthesis or internal fixation device, combined with long-term antibiotic treatment and subsequent indefinite chronic oral antimicrobial suppression (COAS), can be the only reasonable choice. The aim of this study was to investigate the role of COAS and its follow-up in the management of these cases. We retrospectively analyzed a cohort of 16 patients with a follow-up of at least 6 months (mean age 75 yo, 9F, 7M, 11 PJI, 5 FRI). All microbiological isolates were tetracycline-susceptible staphylococci and for this reason a minocycline-based COAS was adopted after debridement and 3 months of antibiogram-guided antibiotic treatment. Patient monitoring was carried out on a clinical basis, with bimonthly execution of the inflammation indices and serial radiolabeled leukocyte scintigraphy (LS). The overall median time of COAS follow-up was 15 months (min 6-max 30). Moreover, 62.5% of patients were still taking COAS with no relapse after cure at the last evaluation available. Clinical failure with a relapse of the infection was observed in 37.5% of patients; interestingly, 50% of them had previously stopped COAS due to side effects of the antibiotic used. In the COAS follow-up, a combination of clinical, laboratory and LS evaluation seems to monitor the infection properly. COAS can be considered as an interesting approach in patients not suitable for standard treatments of PJI or FRI but it requires careful monitoring.

Alterations in the Expression of IFN Lambda, IFN Gamma and Toll-like Receptors in Severe COVID-19 Patients.

Contradictory results have been reported regarding interferon (IFN) lambda (λ1-3) and IFN gamma (γ) production in COVID-19 patients. To gain insight into the roles played by these IFNs in SARS-CoV-2 infection, IFNλ1-3 and IFNγ mRNA expression was evaluated in peripheral blood mononuclear cells (PBMCs) (n = 32) and in cells of paired bronchoalveolar lavages (BALs) (n = 12). Lower IFNλ1-3 values (p < 0.001 for IFNλ1 and 3 and p = 0.013 for IFNλ2) in the PBMCs of severely ill patients were found compared to healthy donors (n = 15). Reduced levels of IFNγ were also detected in patients' PBMCs (p < 0.01) and BALs (p = 0.041) compared to healthy donors. The presence of secondary bacterial infections was associated with decreased IFNλ amounts in PBMCs (p = 0.001, p = 0.015 and p = 0.003, respectively) but increased concentrations of IFNλ3 (p = 0.022) in BALs. Patients with alterations in C-reactive protein, lactate dehydrogenase and D-dimer levels had decreased IFNλ1 and 3 (p = 0.003 and p < 0.001) and increased IFNγ (p = 0.08) in PBMCs. Analyzing Toll-like receptors (TLRs) involved in IFN production, we found that TLR3 was highly expressed (p = 0.033) in patients with bacterial superinfections, while TLR7 and 8 (p = 0.029 and p = 0.049) were reduced in BALs of deceased patients. Overall, severe COVID-19 might be characterized by dysregulation in IFNγ, IFNλ and TLR3, 7 and 8 production.

Cellular Immune Profiling of Lung and Blood Compartments in Patients with SARS-CoV-2 Infection.

BACKGROUND: SARS-CoV-2 related immunopathology may be the driving cause underlying severe COVID-19. Through an immunophenotyping analysis on paired bronchoalveolar lavage fluid (BALF) and blood samples collected from mechanically ventilated patients with COVID-19-associated Acute Respiratory Distress Syndrome (CARDS), this study aimed to evaluate the cellular immune responses in survivors and non-survivors of COVID-19. METHODS: A total of 36 paired clinical samples of bronchoalveolar lavage fluid (BALF) mononuclear cells (BALF-MC) and peripheral blood mononuclear cells (PBMC) were collected from 18 SARS-CoV-2-infected subjects admitted to the intensive care unit (ICU) of the Policlinico Umberto I, Sapienza University Hospital in Rome (Italy) for severe interstitial pneumonia. The frequencies of monocytes (total, classical, intermediate and non-classical) and Natural Killer (NK) cell subsets (total, CD56bright and CD56dim), as well as CD4+ and CD8+ T cell subsets [naïve, central memory (TCM) and effector memory (TEM)], and those expressing CD38 and/or HLADR were evaluated by multiparametric flow cytometry. RESULTS: Survivors with CARDS exhibited higher frequencies of classical monocytes in blood compared to non-survivors (p < 0.05), while no differences in the frequencies of the other monocytes, NK cell and T cell subsets were recorded between these two groups of patients (p > 0.05). The only exception was for peripheral naïve CD4+ T cells levels that were reduced in non-survivors (p = 0.04). An increase in the levels of CD56bright (p = 0.012) and a decrease in CD56dim (p = 0.002) NK cell frequencies was also observed in BALF-MC samples compared to PBMC in deceased COVID-19 patients. Total CD4+ and CD8+ T cell levels in the lung compartment were lower compared to blood (p = 0.002 and p < 0.01, respectively) among non-survivors. Moreover, CD38 and HLA-DR were differentially expressed by CD4+ and CD8+ T cell subsets in BALF-MC and in PBMC among SARS-CoV-2-infected patients who died from COVID-19 (p < 0.05). CONCLUSIONS: These results show that the immune cellular profile in blood and pulmonary compartments was similar in survivors and non-survivors of COVID-19. T lymphocyte levels were reduced, but resulted highly immune-activated in the lung compartment of patients who faced a fatal outcome.

The presence of resistance-associated mutations in reverse transcriptase gene is associated with cerebrospinal fluid HIV-1 escape: A multicentric retrospective analysis.

Higher risk of cerebrospinal fluid escape (CVE) has been associated with the use of specific antiretroviral (ARV) classes, such as protease inhibitors. We assessed whether archived resistance-associated mutations (RAMs) can mediate this relationship by identifying patients treated with incompletely active antiretroviral regimens. A retrospective multicentric study on 282 adult people with HIV on antiretroviral therapy (ART) and available historical plasma genotype resistance testing (HGRT) for reverse transcriptase (RT) and protease genes between 2001 and 2021. The odds ratio for demographic, clinic-, and ART-related variables and CVE was estimated by multivariable modeling. HGRT-adjusted central nervous system effectiveness penetration (CPE) score was computed in modeling the risk. Median age, plasma VL, and CD4 count were 49 years, <50 copies/mL, and 310 cells/µL. CVE was detected in 51 participants (17.0%). No difference in CVE prevalence was observed according to ART type, number of ARVs or ARV classes. Participants with CVE had more frequently plasma (52.9% vs. 32.1%, p = 0.005) and CSF RAMs in RT (n = 63, 57.1% vs. 28.6%, p = 0.029), but not in protease gene. The presence of plasma RAMs in RT associated with increased odds of CVE in adjusted analyses (aOR 3.9, p < 0.001) and in models restricted to plasma viral load ≤50 copies/mL (n = 202; aOR 4.3, p = 0.003). CVE risk decreased by 40% per each point increase in HGRT-adjusted CPE score in multivariable models (p < 0.001). Rather than the type of ARV classes or of ART regimens, functional mono or dual regimens caused by the presence of RAMs affecting ART components may explain the majority of cases of CVE.