Latency reversal agents (LRAs) have proven to induce HIV-1 transcription in vivo but are ineffective at decreasing the size of the latent reservoir in antiretroviral treated patients. The capacity of ...the LRAs to perturb the viral reservoir present in distinct subpopulations of cells is currently unknown. Here, using a new RNA FISH/flow ex vivo viral reactivation assay, we performed a comprehensive assessment of the viral reactivation capacity of different families of LRAs, and their combinations, in different CD4+ T cell subsets. We observed that a median of 16.28% of the whole HIV-reservoir induced HIV-1 transcripts after viral reactivation, but only 10.10% of these HIV-1 RNA+ cells produced the viral protein p24. Moreover, none of the LRAs were powerful enough to reactivate HIV-1 transcription in all CD4+ T cell subpopulations. For instance, the combination of Romidepsin and Ingenol was identified as the best combination of drugs at increasing the proportion of HIV-1 RNA+ cells, in most, but not all, CD4+ T cell subsets. Importantly, memory stem cells were identified as highly resistant to HIV-1 reactivation, and only the combination of Panobinostat and Bryostatin-1 significantly increased the number of cells transcribing HIV within this subset. Overall, our results validate the use of the RNA FISH/flow technique to assess the potency of LRAs among different CD4+ T cell subsets, manifest the intrinsic differences between cells that encompass the latent HIV reservoir, and highlight the difficulty to significantly impact the latent infection with the currently available drugs. Thus, our results have important implications for the rational design of therapies aimed at reversing HIV latency from diverse cellular reservoirs.
The increasing incidence of empyema Burgos, Joaquín; Falcó, Vicenç; Pahissa, Albert
Current opinion in pulmonary medicine
19, Številka:
4
Journal Article
The aim of this review is to highlight recent changes concerning the incidence of empyema. In this article we have focused on community-acquired empyema
The incidence of empyema seems to have been ...increasing both in children and adults worldwide in the past decades, mainly in healthy young adults and in older patients. The bacteriology of pleural infection is changing as well. In children, the most common microorganism that causes empyema continues to be Streptococcus pneumoniae. Interestingly, the widespread use of the seven valent conjugate vaccine has produced a replacement phenomenon with the emergence of some pneumococcal serotypes such as serotypes 1, 3 and 19A, which have a higher propensity to cause empyema. Moreover increases in the incidence of empyema due to Staphylococcus aureus have also been observed. In adults, increases in the rate of empyema due to Streptococcus milleri group and S. aureus have been reported.
Continued surveillance in the epidemiology of empyema is needed. Progress in new strategies of prevention, such as a new generation of conjugate pneumococcal vaccines and protein-based vaccines, could become an important step in the control of this important complication.
Cells that actively transcribe HIV-1 have been defined as the "active viral reservoir" in HIV-infected individuals. However, important technical limitations have precluded the characterization of ...this specific viral reservoir during both treated and untreated HIV-1 infections. Here, we used a novel single-cell RNA fluorescence
hybridization-flow cytometry (FISH-flow) assay that requires only 15 million unfractionated peripheral blood mononuclear cells (PBMCs) to characterize the specific cell subpopulations that transcribe HIV RNA in different subsets of CD4
T cells. In samples from treated and untreated HIV-infected patients, effector memory CD4
T cells were the main cell population supporting HIV RNA transcription. The number of cells expressing HIV correlated with the plasma viral load, intracellular HIV RNA, and proviral DNA quantified by conventional methods and inversely correlated with the CD4
T cell count and the CD4/CD8 ratio. We also found that after
infection of unstimulated PBMCs, HIV-infected T cells upregulated the expression of CD32. In addition, this new methodology detected increased numbers of primary cells expressing viral transcripts and proteins after
viral reactivation with latency reversal agents. This RNA FISH-flow technique allows the identification of the specific cell subpopulations that support viral transcription in HIV-1-infected individuals and has the potential to provide important information on the mechanisms of viral pathogenesis, HIV persistence, and viral reactivation.
Persons infected with HIV-1 contain several cellular viral reservoirs that preclude the complete eradication of the viral infection. Using a novel methodology, we identified effector memory CD4
T cells, immune cells preferentially located in inflamed tissues with potent activity against pathogens, as the main cells encompassing the transcriptionally active HIV-1 reservoir in patients on antiretroviral therapy. Importantly, the identification of such cells provides us with an important target for new therapies designed to target the hidden virus and thus to eliminate the virus from the human body. In addition, because of its ability to identify cells forming part of the viral reservoir, the assay used in this study represents an important new tool in the field of HIV pathogenesis and viral persistence.
The identification of exclusive markers to target HIV-reservoir cells will represent a significant advance in the search for therapies to cure HIV. Here, we identify the B lymphocyte antigen CD20 as ...a marker for HIV-infected cells in vitro and in vivo. The CD20 molecule is dimly expressed in a subpopulation of CD4-positive (CD4
) T lymphocytes from blood, with high levels of cell activation and heterogeneous memory phenotypes. In lymph node samples from infected patients, CD20 is present in productively HIV-infected cells, and ex vivo viral infection selectively upregulates the expression of CD20 during early infection. In samples from patients on antiretroviral therapy (ART) this subpopulation is significantly enriched in HIV transcripts, and the anti-CD20 monoclonal antibody Rituximab induces cell killing, which reduces the pool of HIV-expressing cells when combined with latency reversal agents. We provide a tool for targeting this active HIV-reservoir after viral reactivation in patients while on ART.
We aimed to study the prevalence, characteristics and risk factors of asymptomatic sexually transmitted infections (STIs) in HIV-infected men who have sex with men (MSM). We conducted a prospective ...cross-sectional study, including asymptomatic HIV-infected MSM attending regular visits between December 2014 and December 2017. Of the 301 patients included, 60 patients (19.9%) presented at least one STI. The most common STI was syphilis (33 of 69 STIs), followed by chlamydia (19 of 69), gonorrhoea (10 of 69), hepatitis C virus (4 of 69) and lymphogranuloma venereum (3 of 69). Illicit drug use during sex was the only variable significantly associated with the presence of an STI on multivariate analysis (OR 2.13; 95% CI 1.17-3.89). We were unable to identify a subgroup of patients where we could potentially avoid STI screening. Our findings support current guidelines that recommend routine screening for all HIV-infected MSM regardless of their self-reported sexual history.
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.
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.
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).
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.
•Prevalence of NAFLD is high in this cohort of PLWH according to non-invasive methods.•PLWH exposed to integrase strand transfer inhibitors showed a lower risk for NAFLD.•PLWH with NAFLD exposed to ...thymidine analogues had a higher risk for significant fibrosis.•A lower risk for significant fibrosis was observed in PLWH with NAFLD exposed to NNRTIs.
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.
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.
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.
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.
ABSTRACT
To assess the feasibility of oral fosfomycin-tromethamine (FT) for the management of acute bacterial prostatitis (ABP) caused by multidrug-resistant (MDR) Enterobacterales. An observational ...study of adult patients diagnosed with ABP from Vall d’Hebron University Hospital (Barcelona, Spain), treated with oral FT. The primary outcome was clinical cure defined as symptom relief at the control visit, 2–4 weeks post-end of treatment. Secondary outcomes included microbiological cure, relapse, and adverse events related to the treatment. Eighteen patients with ABP caused by Enterobacterales (15
Escherichia coli
and three
Klebsiella pneumoniae
) were included. Microorganisms were MDR bacteria 14 extended-spectrum beta-lactamase (ESBL) producers and two carbapenemase producing
K. pneumoniae
. Patients received treatment with FT 3 g/48 hours during a median of 14 days (Q25–Q75, 12–17.75). Fifteen patients received a lead-in phase of intravenous suitable antimicrobial during a median of 7 days (Q25–Q75, 3.75–8). No patient had to stop treatment due to adverse events, and the only side effect reported in two patients was diarrhea. Clinical cure was achieved in all (18/18) patients and microbiological cure in 11/12 patients. After a median of follow-up of 5 months (Q25–Q75, 2–11), 2/18 patients relapsed with an orchitis and a new episode of ABP. FT is an attractive step-down therapy for ABP in patients with resistance or side effects to first-line drugs. The availability of oral treatment could reduce the use of the carbapenems, with a benefit in the quality of life of the patient, health costs, and an ecological impact.
IMPORTANCE
We present a brief but largest and interesting experience in which we use fosfomycin-tromethamine (FT) for the treatment of acute bacterial prostatitis (ABP) due to multiresistant bacteria. Our study provides new data that help to consider FT as a plausible alternative for treating ABP in patients with resistance or side effects to first-line drugs. The availability of an alternative oral treatment to avoid the use of the carbapenems could have important benefits in terms of quality of life of the patient, health costs, and an ecological impact.
We present a brief but largest and interesting experience in which we use fosfomycin-tromethamine (FT) for the treatment of acute bacterial prostatitis (ABP) due to multiresistant bacteria. Our study provides new data that help to consider FT as a plausible alternative for treating ABP in patients with resistance or side effects to first-line drugs. The availability of an alternative oral treatment to avoid the use of the carbapenems could have important benefits in terms of quality of life of the patient, health costs, and an ecological impact.
Pneumococcal serotypes are one of the main determinants of pneumococcal disease severity; however, data about their implication in respiratory failure are scarce. We conducted an observational study ...of adults hospitalised with invasive pneumococcal pneumonia to describe the host- and pathogen-related factors associated with respiratory failure. Of 1258 adults with invasive pneumococcal disease, 615 (48.9%) had respiratory failure at presentation. Patients with respiratory failure were older (62.1 years versus 55.4 years, p<0.001) and had a greater proportion of comorbid conditions. They also had a greater proportion of septic shock (41.7% versus 6.1%, p<0.001), required admission to the intensive care unit more often (38.4% versus 4.2%, p<0.001) and had a higher mortality (25.5% versus 3.5%, p<0.001). After adjustment, independent risk factors for respiratory failure were: age >50 years (OR 1.63, 95% CI 1.15-2.3), chronic lung disease (OR 1.54, 95% CI 1.1-2.15), chronic heart disease (OR 1.49, 95% CI 1.01-2.22) and infection caused by serotypes 3 (OR 1.97, 95% CI 1.23-3.16), 19A (OR 2.34, 95% CI 1.14-4.42) and 19F (OR 3.55, 95% CI 1.22-10.28). In conclusion, respiratory failure is a frequent complication of pneumococcal pneumonia and causes high morbidity and mortality. Pneumococcal serotypes 3, 19A and 19F are the main risk factors for this complication.
A higher incidence of malignancies has been described in patients with HIV infection compared to the general population.
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.
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.
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.
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