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We assessed whether symptomatic neurocognitive impairment (NCI) and asymptomatic NCI -of which the clinical relevance is debated- affect HIV control and the role of ART adherence in this relationship. Observational study on the relationship between NCI and viral control during the 2 years before and the 2 after the neurocognitive evaluation (NCE) of 322 PLWH on ART. Viral load (VL) was defined as undetectable, very low-level (VLLV), low-level (LLV), or high-level viremia (HLV), and classified overtime as persistent (p; ≥2 consecutive values in the same worst category), viral failure (VF; ≥1 HLV requiring ART changes), or optimal control. Adherence was the proportion of days covered by ART. Frascati criteria were used. Adjusted models were performed for factors associated with viral control. Mediation analyses informed causality in the path from NCI to viral control through adherence. Sensitivity analyses were focused on the year following NCE for only participants with optimal viral control before. Among the participants (53 ± 10 years, CD4 + T-cells 630/µL), 41.6% and 10.8% presented asymptomatic and symptomatic NCI. Over 3,304 VLs, 8.4% and 22.1% of participants had VF and pLLV/pVLLV. Both symptomatic and asymptomatic NCI were independently associated with VF (aRRR = 8.5; aRRR = 4.3) and pVLLV/pLLV (aRRR = 4.3; aRRR = 2.1). Specific cognitive domains showed independent associations with VL categories (models' P < 0.001). Adherence partially mediated these relationships (models' P < 0.001). Sensitivity analysis confirmed these findings. Prevalence and severity of poor viral control increased as the severity of NCI increased, with ART adherence mediating this relationship. The current "asymptomatic" attribution used by Frascati's criteria could overlook clinical risks.
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Using concentration-time data from the NEAT001/ARNS143 study (single sample at week 4 and 24), we determined raltegravir pharmacokinetic parameters using nonlinear mixed effects modelling (NONMEM v.7.3; 602 samples from 349 patients) and investigated the influence of demographics and SNPs (SLC22A6 and UGT1A1) on raltegravir pharmacokinetics and pharmacodynamics. Demographics and SNPs did not influence raltegravir pharmacokinetics and no significant pharmacokinetic/pharmacodynamic relationships were observed. At week 96, UGT1A1*28/*28 was associated with lower virological failure (p = 0.012), even after adjusting for baseline CD4 count (p = 0.048), but not when adjusted for baseline HIV-1 viral load (p = 0.082) or both (p = 0.089). This is the first study to our knowledge to assess the influence of SNPs on raltegravir pharmacodynamics. The lack of a pharmacokinetic/pharmacodynamic relationship is potentially an artefact of raltegravir's characteristic high inter and intra-patient variability and also suggesting single time point sampling schedules are inadequate to thoroughly assess the influence of SNPs on raltegravir pharmacokinetics.
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Fármacos Anti-VIH , Infecciones por VIH , Humanos , Adulto , Raltegravir Potásico/uso terapéutico , Raltegravir Potásico/farmacología , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Infecciones por VIH/epidemiología , Polimorfismo Genético , Carga Viral/genéticaRESUMEN
Among 128 adult people living with HIV and no neurological conditions confounding the cerebrospinal fluid results, the presence of HSV-1 chronic infection (detected either by serology or PCR), but not of HSV-2 and VZV, independently associated with higher odds of blood-brain barrier impairment, abnormally increased cerebrospinal fluid levels of tau and phosphorylated-181 tau, and decreased concentrations of fragments 1-42 of beta amyloid compared to the seronegative counterpart. These associations were even stronger for seropositive participants with a positive history of at least one symptomatic reactivation of HSV-1.
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Infecciones por VIH , Herpesvirus Humano 1 , Adulto , Humanos , Herpesvirus Humano 1/fisiología , Péptidos beta-Amiloides/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo , Herpesvirus Humano 2 , Barrera Hematoencefálica , Infecciones por VIH/líquido cefalorraquídeoRESUMEN
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.
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AIMS: Antiretroviral (ARV) therapy reduces inflammation and immune activation in people with HIV, but not down to the levels observed in people without HIV. Limited drug penetration within tissues has been argued as a potential mechanism of persistent inflammation. Data on the inflammation role on ARV plasma/intracellular (IC) pharmacokinetics (PK) through to expression of cytochrome P450 3A/membrane transporters are limited. The aim of this study was to investigate the correlation between inflammation markers (IM) and plasma/IC PK of ARV regimen in HIV-positive patients. METHODS: We included ART-experienced patients switching to three different ARV regimens. Plasma and IC ARV drug concentration means at the end of dosing interval (T0 ), IM on samples concomitantly with ARV PK determination: sCD14, CRP, IL-6 and LPS were analysed. RESULTS: Plasma and IC drug concentrations were measured in 60 samples. No significative differences between CRP, sCD14, IL-6 and LPS values in the three arms were observed. A significant inverse correlation between tenofovir plasma concentration and sCD14 (rho = -0.79, P < .001), and between DRV IC/plasma ratio and Log10 IL-6 concentrations (rho = -0.36, P = .040), and a borderline statistically significant positive trend between DRV plasma concentration and sCD14 (rho = 0.31, P = .070) were suggested. Furthermore, a borderline statistically significant inverse trend between DTG IC concentrations and sCD14 (rho = -0.34, P = .090) was observed in 24 patients on DTG-based triple therapy. CONCLUSIONS: Our preliminary data support the hypothesis of lower DRV and DTG IC concentrations and lower TFV plasma exposure in patients with higher plasma IM suggesting an interplay between HIV drug penetration and persistent inflammation in cART-treated HIV-positive patients.
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Fármacos Anti-VIH , Infecciones por VIH , Humanos , Tenofovir/uso terapéutico , Emtricitabina/uso terapéutico , Emtricitabina/farmacocinética , Darunavir , Receptores de Lipopolisacáridos/uso terapéutico , Interleucina-6 , Lipopolisacáridos , Infecciones por VIH/tratamiento farmacológico , Inflamación/tratamiento farmacológicoRESUMEN
Ritonavir-boosted darunavir (DRV/r) and dolutegravir (DTG) are affected by induction of metabolizing enzymes and efflux transporters caused by rifampicin (RIF). This complicates the treatment of people living with HIV (PLWH) diagnosed with tuberculosis. Recent data showed that doubling DRV/r dose did not compensate for this effect, and hepatic safety was unsatisfactory. We aimed to evaluate the pharmacokinetics of DRV, ritonavir (RTV), and DTG in the presence and absence of RIF in peripheral blood mononuclear cells (PBMCs). PLWH were enrolled in a dose-escalation crossover study with 6 treatment periods of 7 days. Participants started with DRV/r 800/100 mg once daily (QD), RIF and DTG were added before the RTV dose was doubled, and then they received DRV/r 800/100 twice daily (BD) and then 1,600/200 QD or vice versa. Finally, RIF was withdrawn. Plasma and intra-PBMC drug concentrations were measured through validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Seventeen participants were enrolled but only 4 completed all study phases due to high incidence of liver toxicity. Intra-PBMC DRV trough serum concentration (Ctrough) after the addition of RIF dropped from a median (interquartile range [IQR]) starting value of 261 ng/mL (158 to 577) to 112 ng/mL (18 to 820) and 31 ng/mL (12 to 331) for 800/100 BD and 1,600/200 QD DRV/r doses, respectively. The DRV intra-PBMC/plasma ratio increased significantly (P = 0.003). DTG and RIF intra-PBMC concentrations were in accordance with previous reports in the absence of RIF or DRV/r. This study showed a differential impact of enzyme and/or transporter induction on DRV/r concentrations in plasma and PBMCs, highlighting the usefulness of studying intra-PBMC pharmacokinetics with drug-drug interactions. (This study has been registered at ClinicalTrials.gov under registration no. NCT03892161.).
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Fármacos Anti-VIH , Infecciones por VIH , Inhibidores de la Proteasa del VIH , Fármacos Anti-VIH/farmacocinética , Cromatografía Liquida , Estudios Cruzados , Darunavir/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/farmacología , Compuestos Heterocíclicos con 3 Anillos , Humanos , Leucocitos Mononucleares , Oxazinas , Piperazinas , Piridonas , Rifampin/farmacocinética , Rifampin/uso terapéutico , Ritonavir/farmacología , Espectrometría de Masas en TándemRESUMEN
Aging and increased cardiovascular risk are major drivers for HIV-associated neurocognitive disorders (HAND), for which accurate screenings are lacking. Mini-Addenbrooke's Cognitive Examination (MACE) reliably detects vascular and neurodegenerative cognitive decline among HIV-negative patients. We evaluated MACE diagnostic accuracy in detecting HAND in people living with HIV (PLWH) and we compared it with the International HIV Dementia Scale (IHDS). A single-centre double-blind study of diagnostic accuracy on adult outpatient PLWH without neurocognitive confounding was performed. MACE and IHDS were administered in 5 and 10 min by clinicians, followed by the reference standard battery (14 tests) by neuropsychologists. HAND diagnosis was based on the modified version of Frascati's criteria by Gisslén to reduce false positives. Exploratory cut-offs were evaluated for MACE. Diagnostic accuracy and clinical utility parameters were assessed. 231 patients were enrolled. 75.7% men with a median age, education, and length of infection of 54 (48-59), 10 (8-13) and 16 (5-25) years. HAND prevalence was 48.5% (38.9% asymptomatic impairment). Compared to IHDS, MACE sensitivity (89.3% vs 70.5%), specificity (94.1% vs 63.0%), correct classification rate (86.5% vs 66.7%), J index (0.83 vs 0.34), AUROC (0.97 vs 0.79), agreement with the gold standard (k 0.84 vs 0.33) and effect size in distinguishing HAND vs non-HAND (d 2.11 vs 1.15) were higher. Among PLWH aged 65 years and above (n = 37) MACE performance was consistently better than IHDS. The quick and easy-to-perform MACE could possess an accurate and useful screening performance for HAND in otherwise neurocognitively healthy cohorts of PLWH.
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Infecciones por VIH , Trastornos Neurocognitivos , Pruebas Neuropsicológicas , Adulto , Envejecimiento , Cognición , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Infecciones por VIH/psicología , Humanos , Masculino , Trastornos Neurocognitivos/diagnóstico , Trastornos Neurocognitivos/epidemiología , Trastornos Neurocognitivos/etiologíaRESUMEN
The aim of this study was to evaluate plasmatic and urinary therapeutic drug monitoring (TDM) of tenofovir disoproxil fumarate (TDF) in a cohort of patients with chronic hepatitis B (CHB). In 68 enrolled patients, the estimated glomerular filtration rate (eGFR) was 68 mL/min in naive subjects, while in adefovir dipivoxil (ADV)-pretreated patients, it was 55.5 mL/min (p < 0.001). The HBV E genotype was associated with lower TDF levels (ß = -0.698, p < 0.001). The urinary TDF concentration was associated with ADV pretreatment (ß = 0.829, p < 0.001). Determination of urinary concentrations of TDF may be useful in the clinical management of older CHB patients and those with previous treatment with ADV.
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Hepatitis B Crónica , Antivirales/farmacología , ADN Viral/genética , Farmacorresistencia Viral , Quimioterapia Combinada , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Tenofovir/uso terapéutico , Resultado del Tratamiento , Carga ViralRESUMEN
The experience gained over the last hundred years clearly indicates that two groups of viruses represent the main risk for the development of highly transmissible epidemics and pandemics in the human species: influenza viruses and coronaviruses (CoV). Although the search for viruses with pandemic potential in the environment may have an important predictive and monitoring role, it is still based on empirical methodologies, mostly resulting from the clinic and not fully validated for environmental matrices. As far as the SARS-CoV-2 pandemic, currently underway, is concerned, environmental monitoring activities aiming at checking the presence of SARS-CoV-2 in wastewater can be extremely useful to predict and check the diffusion of the disease. For this reason, the present study aims at evaluating the SARS-CoV-2 diffusion by means of a wastewater-based environmental monitoring developed in Piedmont, N-W Italy, during the second and third pandemic waves. Wastewater sampling strategies, sampling points sample pre-treatments and analytical methods, data processing and standardization, have been developed and discussed to give representative and reliable results. The following outcomes has been highlighted by the present study: i) a strong correlation between SARS-CoV-2 concentration in untreated wastewater and epidemic evolution in the considered areas can be observed as well as a predictive potential that could provide decision-makers with indications to implement effective policies, to mitigate the effects of the ongoing pandemic and to prepare response plans for future pandemics that could certainly arise in the decades to come; ii) moreover, the data at disposal from our monitoring campaign (almost 500 samples analysed in 11 months) confirm that SARS-CoV-2 concentrations in wastewater are strongly variable and site-specific across the region: the highest SARS-CoV-2 concentration values have been found in sewer networks serving the most populated areas of the region; iii) normalization of viral concentrations in wastewater through Pepper Mild Mottle Virus (a specific faecal marker) has been carried out and commented; iv) the study highlights the potential of wastewater treatment plants to degrade the genetic material referable to SARS-CoV-2 as well. In conclusion, the preliminary data reported in the present paper, although they need to be complemented by further studies considering also other geographical regions, are very promising.
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COVID-19 , Aguas Residuales , Monitoreo del Ambiente , Humanos , Italia/epidemiología , SARS-CoV-2RESUMEN
In vitro and animal models described lower replication capacity and virulence of SARS-CoV-2 Omicron lineage in lower respiratory airways compared to wild type and other variants of concern (oVOCs). Among adult subjects admitted to our hospital (Turin, Italy) due to wild type, oVOCs, and Omicron SARS-CoV-2-related pneumonia (n = 100 for each lineage), the cases of Omicron pneumonia showed lower degree of lung parenchyma involvement (aß -1.471, p = 0.037), less tendency to parenchyma consolidation (aOR 0.500, p = 0.011), and better respiratory functions (assessed by ambient air arterial blood gas analysis). After adjusting for demographic, previous immunity, and comorbidities, Omicron pneumonia still associated with lower risk of respiratory failure (for severe respiratory failure, Wild-type versus Omicron aOR 15.6, p = 0.005 and oVOCs versus Omicron aOR 31.7, p < 0.001). These observations are in line with preliminary findings from in vitro and animal models and could explain why Omicron infection has been associated with lower mortality and hospitalization in human.
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COVID-19 , Neumonía , Insuficiencia Respiratoria , Animales , Humanos , Pacientes Internos , Pulmón , SARS-CoV-2 , VirulenciaRESUMEN
OBJECTIVE(S): This prospective observational cohort study aimed to evaluate whether women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the first trimester of pregnancy are at higher risk of adverse obstetric and neonatal outcomes compared to negative patients. STUDY DESIGN: Seromolecular testing for SARS-CoV-2 was performed at 12, 16, 21 weeks, and at delivery; the cohort was then subdivided into a first-trimester SARS-CoV-2-positive (case) group and a SARS-CoV-2-negative (control) group. The primary outcome was a composite adverse obstetric outcome, defined as the presence of either abortion, preterm delivery, preterm prelabor rupture of membranes, preeclampsia, intrauterine growth restriction, stillbirth; and a composite measure of adverse neonatal events, including either 1- and 5-min Apgar score ≤ 7, neonatal intensive care unit admission and congenital birth defects. Maternal symptoms and antibody titer were secondarily assessed. RESULTS: A total of 17 of 164 women tested positive for SARS-CoV-2 (10.3%) in the first trimester. One SARS-CoV-2-positive patient who gave birth at another hospital was excluded. Composite adverse obstetric outcome was observed in 6.2% (1/16) SARS-CoV-2-positive and 10.5% (11/105) SARS-CoV-2-negative women; composite adverse neonatal outcome in 12.5% (2/16) and 7.6% (8/105), respectively. In the newborns of women who had developed IgG antibodies, the same antibodies were detected in arterial cord blood and the nasopharyngeal swab tested negative for SARS-CoV-2. No maternal pneumonia or hospital admission due to coronavirus disease-19 were recorded. CONCLUSION: Asymptomatic or mildly symptomatic women during the first trimester of pregnancy did not experience significantly more adverse events than SARS-CoV-2-negative women.
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COVID-19 , Complicaciones Infecciosas del Embarazo , Nacimiento Prematuro , Femenino , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/epidemiología , Resultado del Embarazo , Primer Trimestre del Embarazo , Estudios Prospectivos , SARS-CoV-2RESUMEN
Bacteria biofilm consists of microorganisms, accounting for 5-35% of the biofilm volume, and of the extracellular matrix (65-95%), made of water (97%), proteins (2%), polysaccharides (1-2%) and nucleic acids (DNA/RNA, both <1%). The physiology of bacteria in the biofilms entails adaptive changes with expression of genes which are different from those translated in the planktonic state. While most of our applied knowledge on bacterial biology stems from the study in the planktonic state, an increasing interest is currently paid to bacterial behaviour as biofilm generators, as it is estimated that 65% of all bacterial infections are associated with bacterial biofilms. Infections of both upper and lower airways, bacterial endocarditis, chronic otitis media, urinary tract infections, periodontitis, ocular infections and chronic wound infections (including diabetic foot ulcer) are all associated with biofilm formation. The role of biofilm is also relevant in case of infections taking place on abiotic surfaces, as in the case of infections occurring on prostheses and several other medical devices. Here, we review current knowledge on biofilm formation and its impact on human infections, discussing recent means for its inhibition, with particular emphasis on an interesting anti-biofilm activity exerted by exopolysaccharides derived from marine strains of Bacillus licheniformis.
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Infecciones Bacterianas , Biopelículas , Humanos , BacteriasRESUMEN
This study aimed to develop a new approach to manage people living with HIV (PLWH), investigating preferences of clinicians and PLWH in order to improve linkage to care of PLWH. A survey was performed with the Discrete Choice Experiment (DCE) method to investigate the preferences of two categories, clinicians and PLWH, for attributes of HIV care pathways, therapy and quality of life. Our results suggest that the most important feature of a care pathway was the site of testing for both categories, followed by modality of counselling for clinicians and by pre-exposure prophylaxis for PLWH. Regarding therapy, choices were mostly oriented by modality of administration for both categories, and by CD4 cells increase for clinicians and side effects for PLWH. People living with HIV reported that, out of 13 candidates, the two most important factors related to good long-term quality of life would be reduction of viral transmissibility and good emotional life. A tailored approach could be the key to long-term treatment success, but this approach must necessarily be based on evaluation of the specific complexities of the patient.
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Infecciones por VIH , Calidad de Vida , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Encuestas y CuestionariosRESUMEN
We measured severe acute respiratory syndrome coronavirus 2 spike protein subunits S1/S2 antibodies by using capillary electrophoresis and a chemiluminescence immunoassay for 5,444 active healthcare workers in Italy. Seroprevalence was 6.9% and higher among participants having contact with patients. Seroconversion was not observed in 37/213 previously infected participants.
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COVID-19/epidemiología , Personal de Salud , SARS-CoV-2 , Humanos , Italia/epidemiologíaRESUMEN
Four pre-exposure prophylaxis (PrEP) users with gastro-intestinal disorders (sleeve gastrectomy, terminal ileitis, celiac disease or chronic diarrhea) and receiving oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) were included. Despite a self-reported high adherence, trough plasma tenofovir concentrations (after a supervised intake) were significantly lower than those observed in PrEP recipients without gastrointestinal disorders [21 (±9.1) vs. 138 (±85) ng/mL]. PrEP users with gastrointestinal disorders may need increased TDF doses or alternative prophylactic measures.
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Congenitally- or perinatally-acquired viral infections can be harmful to the fetus but data are limited about prevalence and outcomes of coronavirus disease 2019 (COVID-19) disease during the first trimester of pregnancy. We report epidemiologic data from a study investigating a cohort of women who became pregnant just before or during the COVID-19 pandemic. We recruited 138 consecutive pregnant women attending for first trimester screening (11-13 weeks of gestation) at Sant'Anna Hospital, Turin, Piedmont, Italy, during the plateau and the falling phase of the COVID-19 epidemic curve. Patients were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin M/immunoglobulin G antibody levels and SARS-CoV-2 detection in sera and nasopharyngeal swab samples. COVID-19 cumulative incidence during the first trimester was of 10.1% with high prevalence of asymptomatic patients (42.8%). Similar to the course of the disease in non pregnant adults, 80% to 90% of infections were not severe.The prevalence of reported symptoms was four-fold higher in SARS-CoV-2 positive patients (57%) than in those negative (13%) (P < .001), suggesting that direct self-testing should open doors to confirmatory testing for COVID-19. Our findings support the need for COVID-19 screening in early pregnancy in epidemic areas to plan materno-fetal health surveillance programs.
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COVID-19 , Complicaciones Infecciosas del Embarazo/virología , Primer Trimestre del Embarazo , SARS-CoV-2 , Adulto , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , COVID-19/epidemiología , Estudios de Cohortes , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Incidencia , Italia/epidemiología , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Prevalencia , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificaciónRESUMEN
BACKGROUND: The disease caused by the severe acute respiratory syndrome coronavirus 2 was named coronavirus disease 2019 and classified as a global public health emergency. The evidence related to the impact of coronavirus disease 2019 on pregnancy is limited to the second and third trimester of pregnancy, whereas data on the first trimester are scant. Many viral infections can be harmful to the fetus during the first trimester of pregnancy, and whether severe acute respiratory syndrome coronavirus 2 is one of them is still unknown. OBJECTIVE: With this study, we evaluated severe acute respiratory syndrome coronavirus 2 infection as a risk factor for early pregnancy loss in the first trimester of pregnancy. Furthermore, coronavirus disease 2019 course in the first trimester was assessed. STUDY DESIGN: Between February 22 and May 21, 2020, we conducted a case-control study at S. Anna Hospital, Turin, among pregnant women in their first trimester, paired for last menstruation. The cumulative incidence of coronavirus disease 2019 was compared between women with spontaneous abortion (case group, n=100) and those with ongoing pregnancy (control group, n=125). Current or past infection was determined by the detection of severe acute respiratory syndrome coronavirus 2 from nasopharyngeal swab and severe acute respiratory syndrome coronavirus 2 immunoglobulin G and immunoglobulin M antibodies in a blood sample. Patient demographics, coronavirus disease 2019-related symptoms, and the main risk factors for abortion were collected. RESULTS: Of 225 women, 23 (10.2%) had a positive test result for coronavirus disease 2019. There was no difference in the cumulative incidence of coronavirus disease 2019 between the cases (11/100, 11%) and the controls (12/125, 9.6%) (P=.73). Logistic regression analysis confirmed that coronavirus disease 2019 was not an independent predictor of early pregnancy loss (odds ratio, 1.28; confidence interval, 0.53-3.08). Coronavirus disease 2019-related symptoms in the first trimester were fever, anosmia, ageusia, cough, arthralgia, and diarrhea; no cases of pneumonia or hospital admission owing to coronavirus disease 2019-related symptoms were recorded. No difference in the incidence of symptoms was noted between the 2 groups. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during the first trimester of pregnancy does not seem to predispose to early pregnancy loss; its cumulative incidence did not differ between women with spontaneous abortion and women with ongoing pregnancy. Coronavirus disease 2019 appears to have a favorable maternal course at the beginning of pregnancy, consistent with what has been observed during the second and third trimesters.
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Aborto Espontáneo/etiología , COVID-19/complicaciones , Complicaciones Infecciosas del Embarazo , SARS-CoV-2 , Adulto , Anticuerpos Antivirales/sangre , Estudios de Casos y Controles , Femenino , Humanos , Modelos Logísticos , Embarazo , Primer Trimestre del Embarazo , SARS-CoV-2/inmunologíaRESUMEN
AIM: People living with HIV (PLWH) have a high burden of comorbidities and concomitant medication use. The aim of this study was to analyse the prevalence, predictors and patterns of polypharmacy (PP) in a large therapeutic drug monitoring (TDM) registry. METHODS: We searched our TDM registry and categorized co-medications into 26 drug classes. We included patients with at least one medication recorded: PP and severe polypharmacy (sPP) were defined as the concomitant use of ≥5 or ≥10 nonantiretroviral/nonantitubercular drugs. Multivariable binary logistic analysis were conducted for identifying PP/sPP predictors. A hierarchical average-linkage cluster analysis was performed among drug classes. RESULTS: We included 2432 participants (1158 PLWH) aged 49.6 years (± 14.4) in the 2016-2020 period. A higher number of concomitant medications (4 vs 3.1, P < .001) and a higher prevalence of PP (26.1% vs 21.8%, P = .015) were recorded in controls. At multivariable binary logistic analysis older age, female gender and HIV-positive serostatus (P = .015) were independent predictors of PP; older age and year of inclusion were independent predictors of sPP. Cluster analysis showed that patients receiving oral drug for type 2 diabetes have a high probability of receiving several other drugs; a cluster of co-medications was observed with opioids, diuretics and central nervous system-affecting drugs. CONCLUSION: We observed a moderately high prevalence of polypharmacy in middle-aged PLWH: advanced age and female gender were associated with the greatest prevalence. The observation of co-medication clusters suggests groups of comorbidities but also identifies groups of patients at risk of similar drug-to-drug interactions.
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Diabetes Mellitus Tipo 2 , Infecciones por VIH , Anciano , Análisis por Conglomerados , Estudios Transversales , Monitoreo de Drogas , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Persona de Mediana Edad , PolifarmaciaRESUMEN
Remdesivir is one of the most encouraging treatments against SARS-CoV-2 infection. After intravenous infusion, RDV is rapidly metabolized (t1/2 = 1 h) within the cells to its active adenosine triphosphate analogue form (GS-443902) and then it can be found in plasma in its nucleoside analogue form (GS-441524). In this real-life study, we describe the remdesivir and GS-441524 concentrations at three time points in nine ICU patients, through a validated ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method. The observed data confirmed the very rapid conversion of RDV to its metabolite and the quite long half-life of GS-441524. The mean Cmin , Cmax and AUC0-24 , were < 0.24 ng/mL and 122.3 ng/mL, 2637.3 ng/mL and 157.8 ng/mL, and 5171.2 ng*h/mL and 3676.5 ng*h/ml, respectively, for RDV and GS-441524. Three out of nine patients achieved a Cmax > 2610 ng/mL and 140 ng/mL and AUC0-24 > 1560 ng*h/mL and 2230 ng*h/mL for RDV and GS-441524, respectively. The mean t1/2 value for GS-441524 was 26.3 h. Despite the low number of patients, these data can represent an interesting preliminary report on the variability of RDV and GS-441524 concentrations in a real-life ICU setting.
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Tratamiento Farmacológico de COVID-19 , Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Antivirales/uso terapéutico , Humanos , Unidades de Cuidados Intensivos , SARS-CoV-2 , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: Tuberculous meningitis (TBM) is an important disease leading to morbidity, disability and mortality that primarily affects children and immune-depressed patients. Specific neuromarkers predicting outcomes, severity and inflammatory response are still lacking. In recent years an increasing number of evidences show a possible role for infective agents in developing neurodegenerative diseases. METHODS: We retrospectively included 13 HIV-negative patients presenting with TBM and we compared them with two control groups: one of patients with a confirmed diagnosis of AD, and one of those with syphilis where lumbar punctures excluded central nervous system involvement. Lumbar punctures were performed for clinical reasons and CSF biomarkers were routinely available: we analyzed blood brain barrier permeability (CSF to serum albumin ratio, "CSAR"), intrathecal IgG synthesis, (CSF to serum IgG ratio), inflammation (neopterin), amyloid deposition (Aß1-42), neuronal damage (T-tau, P-tau, 14.3.3) and astrocytosis (S-100 ß). RESULTS: TBM patients were 83 % male and 67 % Caucasian with a median age of 51 years (24.5-63.5 IQR). Apart from altered CSAR (median value 18.4, 17.1-30.9 IQR), neopterin (14.3 ng/ml, 9.7-18.8) and IgG ratios (15.4, 7.9-24.9), patients showed very low levels of Aß1-42 in their CSF (348.5 pg/mL,125-532.2), even lower compared to AD and controls [603 pg/mL (IQR 528-797) and 978 (IQR 789-1178)]. Protein 14.3.3 tested altered in 38.5 % cases. T-tau, P-tau and S100Beta were in the range of normality. Altered low level of Aß1-42 correlated over time with classical TBM findings and altered neuromarkers. CONCLUSIONS: CSF Biomarkers from patients with TBM were compatible with inflammation, blood brain barrier damage and impairment in amyloid-beta metabolism. Amyloid-beta could be tested as a prognostic markers, backing the routine use of available neuromarkers. To our knowledge this is the first case showing such low levels of Aß1-42 in TBM; its accumulation, drove by neuroinflammation related to infections, can be central in understanding neurodegenerative diseases.