ABSTRACT
BACKGROUND: Both fidaxomicin and bezlotoxumab (used in combination with an antibiotic against Clostridioides difficile) achieve reductions in recurrence rates of C. difficile infection (CDI). However, the two strategies have never been compared. METHODS: Data from two retrospective cohorts of 'real-life' use of fidaxomicin and bezlotoxumab in combination with a standard anti-C. difficile antibiotic were used to compare the rates of recurrence of both strategies. Since the two cohorts were not identical, we used a propensity score analysis. RESULTS: Three hundred and two patients were included: 244 in the fidaxomicin cohort and 78 in the bezlotoxumab cohort. A history of renal failure or immunosuppression was more frequent in patients receiving bezlotoxumab (39.7% and 66.7% versus 26.6% and 38.9%; Pâ=â0.03 and Pâ<â0.001, respectively), but the severity and number of previous CDI episodes were similar in both cohorts. We observed that 19.3% of the patients in the fidaxomicin cohort experienced recurrence, compared with 14.1% in the bezlotoxumab cohort (OR 1.45; 95% CI 0.71-2.96; Pâ=â0.29) but the difference remained non-significant after propensity score matching using previously defined variables (OR 1.24; 95% CI 0.50-3.07; Pâ=â0.64). Moreover, the multivariate analysis did not show differences depending on the drug used. CONCLUSIONS: We observed that fidaxomicin and bezlotoxumab are prescribed in similar clinical scenarios, although those treated with bezlotoxumab have greater comorbidity. The proportion of recurrences was numerically lower in those treated with bezlotoxumab, although the propensity analysis did not find significant differences between the two drugs.
Subject(s)
Clostridium Infections , Vancomycin , Anti-Bacterial Agents/therapeutic use , Antibodies, Monoclonal , Broadly Neutralizing Antibodies , Clostridium Infections/drug therapy , Cohort Studies , Fidaxomicin/therapeutic use , Humans , Recurrence , Retrospective Studies , Treatment Outcome , Vancomycin/therapeutic useABSTRACT
OBJECTIVES: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. METHODS: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. RESULTS: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). CONCLUSIONS: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population.
Subject(s)
Coinfection , HIV Infections , Hepatitis C, Chronic , Hepatitis C , Antiviral Agents/therapeutic use , Coinfection/drug therapy , Coinfection/epidemiology , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Hepacivirus/genetics , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Humans , Liver Cirrhosis/epidemiology , RNA/therapeutic use , Spain/epidemiologyABSTRACT
The high cost of fidaxomicin has restricted its use despite the benefit of a lower Clostridioides difficile infection (CDI) recurrence rate at 4 weeks of follow-up. This short follow-up represents the main limitation of pivotal clinical trials of fidaxomicin, and some recent studies question its benefits over vancomycin. Moreover, the main risk factors of recurrence after treatment with fidaxomicin remain unknown. We designed a multicentre retrospective cohort study among four Spanish hospitals to assess the efficacy of fidaxomicin in real life and to investigate risk factors of fidaxomicin failure at weeks 8 and 12. Two-hundred forty-four patients were included. Fidaxomicin was used in 96 patients (39.3%) for a first episode of CDI, in 95 patients (38.9%) for a second episode, and in 53 patients (21.7%) for a third or subsequent episode. Patients treated with fidaxomicin in a first episode were younger (59.9 years vs 73.5 years), but they had more severe episodes (52.1% vs. 32.4%). The recurrence rates for patients treated in the first episode were 6.5% and 9.7% at weeks 8 and 12, respectively. Recurrence rates increased for patients treated at second or ulterior episodes (16.3% and 26.4% at week 8, respectively). Age greater than or equal to 85 years and having had a previous episode of CDI were identified as recurrence risk factors at weeks 8 and 12. We conclude that the outcomes with fidaxomicin in real life are at least as good as those observed in clinical trials despite a more demanding evaluation. Be it 85 years of age or older, and the use after a first episode appears to be independent factors of CDI recurrence after treatment with fidaxomicin.
Subject(s)
Clostridioides difficile , Clostridium Infections , Anti-Bacterial Agents/therapeutic use , Clostridioides , Clostridium Infections/drug therapy , Cohort Studies , Fidaxomicin , Humans , Recurrence , Retrospective StudiesABSTRACT
OBJECTIVE: HIV infection is associated with an increased risk of cardiovascular disease. Irisin is a miokyne secreted by skeletal muscle, which may influence insulin homeostasis, nonalcoholic fatty liver disease (NAFLD) and atherosclerosis. Our objective was to evaluate the relationships between serum irisin, insulin homeostasis, NAFLD and subclinical atherosclerosis in HIV-infected males. DESIGN: Cross-sectional study in a cohort of HIV-infected patients. PATIENTS: Inclusion criteria: men older than 18 years; antiretroviral therapy (ART) -naïve or on effective ART (<50 HIV-1 RNA copies/mL) without changes in the previous 6 months; no diabetes or hepatitis C. MEASUREMENTS: Irisin was measured by enzymatic immunoassay (Phoenix Pharmaceuticals), insulin sensitivity by homeostasis model assessment of insulin resistance (HOMA-IR), as well as the 2-hour continuous infusion of glucose with model assessment (CIGMA-HOMA). Hepatic steatosis was measured by 1-H magnetic resonance spectroscopy, subclinical atherosclerosis by evaluation of carotid intima-media thickness (C-IMT), measured by Ultrasonography. RESULTS: Eight nine men (age 42.0 ± 8.3 years, duration of HIV infection 7.9 ± 5.6 years, CD4 count 547 ± 279 cells/mL) were included. Circulating irisin was positively related to HOMA-IR and CIGMA-HOMA, hepatic triglyceride content, and to VAT/SAT ratio. Higher irisin concentrations were associated with higher C-IMT, although this association did not persist in multivariate analysis. Lipodystrophy and a higher baseline PAI-1 concentration were independently associated with C-IMT. CONCLUSIONS: In male HIV patients without diabetes, higher irisin concentrations are positively associated with insulin resistance, NAFLD and subclinical atherosclerosis. However, waist-hip-ratio is the main determinant of insulin resistance, and PAI-1 and lipodystrophy were the strongest determinants of IMT in this population.
Subject(s)
Atherosclerosis/blood , Fibronectins/blood , HIV Infections/blood , Non-alcoholic Fatty Liver Disease/blood , Adult , Carotid Intima-Media Thickness , Cross-Sectional Studies , Humans , Insulin Resistance/physiology , Magnetic Resonance Spectroscopy , Male , Middle AgedABSTRACT
BACKGROUND: Pathogenesis of atherosclerosis is complex, and differences between HIV-infected patients and general population cannot be completely explained by the higher prevalence of traditional cardiovascular risk factors. We aimed to analyse the association between inflammation and subclinical atherosclerosis in HIV patients with low Framingham risk score. MATERIALS AND METHODS: Case-control study. SETTING: Outpatient Infectious Diseases clinic in a university hospital. SUBJECTS: HIV-1-infected patients aged > 35 years receiving antiretroviral treatment with viral load < 50 copies/mL and Framingham risk score < 10%. EXCLUSION CRITERIA: inflammatory diseases; dyslipidaemia requiring statins; smoking > 5 cigarettes/day; diabetes; hypertension; vascular diseases. MAIN OUTCOME: subclinical atherosclerosis determined by ultrasonography: common carotid intima-media thickness greater than 0·8 mm or carotid plaque presence. Explanatory variables: ribosomal bacterial DNA (rDNA), sCD14, interleukin-6 (IL-6) and TNF-α. RESULTS: Eighty-four patients were included, 75% male, mean age 42 years and mean CD4+ cells 657 ± 215/mm3 . Median Framingham risk score was 1% at 10 years (percentile 25-75: 0·5-4%). Eighteen patients (21%) had subclinical atherosclerosis; the associated factors were older age (P = 0·001), waist-hip ratio (P = 0·01), time from HIV diagnosis (P = 0·02), rDNA (P = 0·04) and IL-6 (P = 0·01). In multivariate analysis, OR for subclinical atherosclerosis was 7 (95% CI, 1.3-40, P = 0.02) and 9 (95% CI, 1.0-85, P = 0.04) for patients older than 44 years and IL-6 > 6·6 pg/mL, respectively. CONCLUSIONS: Well-controlled HIV patients with low Framingham risk score have a high prevalence of subclinical carotid atherosclerosis, and the main risk factors are age and inflammation. These patients are not receiving primary prophylaxis for cardiovascular events according to current guidelines.
Subject(s)
Anti-HIV Agents/therapeutic use , Carotid Artery Diseases/virology , HIV Infections/drug therapy , Adult , Age Factors , Biomarkers/metabolism , Body Mass Index , Carotid Artery Diseases/diagnostic imaging , Carotid Intima-Media Thickness , Case-Control Studies , DNA, Ribosomal/metabolism , Female , Humans , Interleukin-6/metabolism , Lipopolysaccharide Receptors/metabolism , Male , Risk Factors , Viral LoadABSTRACT
OBJECTIVES: To evaluate the liver safety of raltegravir-including combinations in HIV/hepatitis C virus (HCV) co-infected patients. METHODS: Grade 3-4 transaminase elevations (TEs) and grade 4 total bilirubin elevations (TBEs) were assessed during 12 months in 108 HIV/HCV co-infected patients starting antiretroviral therapy including raltegravir in a retrospective cohort study. Furthermore, the relationship between baseline fibrosis and hepatotoxic events was determined. RESULTS: Eight patients (7.4%) developed grade 3 TEs and two (1.9%) patients showed grade 4 TEs. TBE grade 4 was detected in two (1.9%) patients. No patient permanently discontinued raltegravir because of hepatotoxic events. Of the patients with and without significant fibrosis, six (9.4%) and two (11.8%), respectively, showed grade 3-4 TEs (Pâ=â0.769). Grade 3-4 TEs was observed in four (9.8%) patients in whom cirrhosis was ruled out, while none of the patients diagnosed with cirrhosis developed grade 3-4 TEs (Pâ=â0.303). During the follow-up, the median (Q1-Q3) CD4 cell count increased from 257 (145-421) cells/mm(3) to 407 (213-587) cells/mm(3) (Pâ<â0.0001) and the number of patients with an undetectable HIV viral load augmented from 33 (30.6%) to 73 (81.1%) (Pâ=â0.002). CONCLUSIONS: Raltegravir-containing regimens are safe in HIV/HCV co-infected patients. The incidence of severe liver toxicity of raltegravir in these individuals is in the range of boosted protease inhibitors in clinical trials. The frequencies of grade 3-4 TEs and grade 4 TBEs were similar in patients receiving raltegravir with or without significant fibrosis or cirrhosis.
Subject(s)
Anti-HIV Agents/adverse effects , Antiretroviral Therapy, Highly Active/adverse effects , HIV Infections/complications , HIV Infections/drug therapy , Hepatitis C, Chronic/pathology , Liver/drug effects , Pyrrolidinones/adverse effects , Adult , Anti-HIV Agents/administration & dosage , Antiretroviral Therapy, Highly Active/methods , Bilirubin/blood , Cohort Studies , Female , Humans , Liver Cirrhosis/pathology , Liver Function Tests , Male , Middle Aged , Pyrrolidinones/administration & dosage , Raltegravir Potassium , Retrospective Studies , Transaminases/bloodABSTRACT
BACKGROUND: Although the association between HIV infection and airways obstruction is well known, its etiopathogenesis is not clear. OBJECTIVES: Our aim was to analyze the association between biomarkers of systemic inflammation and bacterial translocation and pulmonary function tests in HIV infected patients and compare it between smokers and non-smokers. METHODS: Cross-sectional, observational study. Inclusion criteria: people living with HIV with undetectable plasma viral load. Exclusion criteria: other comorbidities associated with systemic inflammation. Outcome variables: spirometry and diffusing capacity for carbon monoxide; explanatory variables: inflammatory biomarkers (interleukin-6, tumor necrosis factor-alpha), bacterial translocation (soluble CD14 [sCD14] and bacterial 16S rDNA), and variables related to HIV infection. Associations were tested using the Pearson/Spearman correlation tests, the student t test, and multivariable linear regression. RESULTS: We included 71 patients (54.9% smokers). We did not observe significant differences in pulmonary function tests according to biomarkers of inflammation or bacterial translocation. In non-smokers (n=32), sCD14 was negatively correlated with forced expiratory volume in 1 second (R = -0.35, P = 0.048) and forced vital capacity (R= -0.40, P=0.023). Age, time since HIV diagnosis and CD4+ nadir were associated with alterations in PFTs. In smokers, the only association observed was between the pack-years and pulmonary obstruction. CONCLUSION: In non-smokers HIV patients, lung dysfunction can be, at least partially, related to bacterial translocation (sCD14), CD4+ nadir and time since HIV diagnosis.
Subject(s)
HIV Infections , Bacterial Translocation , Biomarkers , Cross-Sectional Studies , HIV Infections/pathology , Humans , Viral LoadABSTRACT
The aim of this study is to examine the reproductive history of human immunodeficiency virus (HIV)-positive women, before and after HIV diagnosis, to describe the characteristics of women with pregnancies after HIV diagnosis, and to assess the prevalence of mother-to-child transmission.A cross-sectional study was performed among women within reproductive ages (18-49) selected from the cohort in the Spanish AIDS Research Network (CoRIS). A descriptive analysis of the pregnancy outcomes was made according to women's serostatus at the moment of pregnancy and association of women's characteristics with having pregnancy after HIV diagnosis was evaluated using logistic regression models.Overall, 161 women were interviewed; of them, 86% had been pregnant at least once and 39% after HIV diagnosis. There were 347 pregnancies, 29% of them occurred after HIV diagnosis and in these, 20% were miscarriages and 29% were voluntary termination of pregnancy. There were 3 cases of mother-to-child transmission among the 56 children born from HIV-positive mothers; in these cases, women were diagnosed during delivery. Having a pregnancy after HIV diagnosis was more likely when the younger women were at the time of diagnosis: odds ratio (OR)â=â1.29 (95% confidence interval 0.40-4.17) for 25 to 29 years old, ORâ=â0.59 (0.15-2.29) for 30 to 34 years old, ORâ=â0.14 (0.03-0.74) for ≥35 years old, compared with those <25 years at diagnosis, who were diagnosed for ≥5 years (ORâ=â5.27 [1.71-16.18]), who received antiretroviral treatment at some point (ORâ=â9.38 [1.09-80.45]), and who received information on reproductive health (ORâ=â4.32 [1.52-12.26]).An important number of pregnancies occurred after HIV diagnosis, reflecting a desire for motherhood in these women. Reproductive and sexual health should be tackled in medical follow-ups.
Subject(s)
HIV Infections/complications , HIV Seropositivity/complications , Infectious Disease Transmission, Vertical/statistics & numerical data , Pregnancy Complications, Infectious/epidemiology , Reproductive History , Adolescent , Adult , Cross-Sectional Studies , Female , HIV Infections/epidemiology , HIV Infections/virology , HIV Seropositivity/epidemiology , HIV Seropositivity/virology , Humans , Middle Aged , Odds Ratio , Pregnancy , Pregnancy Complications, Infectious/virology , Pregnancy Outcome , Prevalence , Spain/epidemiology , Young AdultABSTRACT
INTRODUCTION: Vitamin D insufficiency (VDI) has been associated with increased cardiovascular risk in the non-HIV population. This study evaluates the relationship among serum 25-hydroxyvitamin D [25(OH)D] levels, cardiovascular risk factors, adipokines, antiviral therapy (ART) and subclinical atherosclerosis in HIV-infected males. METHODS: A cross-sectional study in ambulatory care was made in non-diabetic patients living with HIV. VDI was defined as 25(OH)D serum levels <75 nmol/L. Fasting lipids, glucose, inflammatory markers (tumour necrosis factor-α, interleukin-6, high-sensitivity C-reactive protein) and endothelial markers (plasminogen activator inhibitor-1, or PAI-I) were measured. The common carotid artery intima-media thickness (C-IMT) was determined. A multivariate logistic regression analysis was made to identify factors associated with the presence of VDI, while multivariate linear regression analysis was used to identify factors associated with common C-IMT. RESULTS: Eighty-nine patients were included (age 42 ± 8 years), 18.9% were in CDC (US Centers for Disease Control and Prevention) stage C and 75 were on ART. VDI was associated with ART exposure, sedentary lifestyle, higher triglycerides levels and PAI-I. In univariate analysis, VDI was associated with greater common C-IMT. The multivariate linear regression model, adjusted by confounding factors, revealed an independent association between common C-IMT and patient age, time of exposure to protease inhibitors (PIs) and impaired fasting glucose (IFG). In contrast, there were no independent associations between common C-IMT and VDI or inflammatory and endothelial markers. CONCLUSIONS: VDI was not independently associated with subclinical atherosclerosis in non-diabetic males living with HIV. Older age, a longer exposure to PIs, and IFG were independent factors associated with common C-IMT in this population.
Subject(s)
Atherosclerosis/etiology , HIV Infections/complications , Vitamin D Deficiency/complications , Adult , Asymptomatic Diseases/epidemiology , Blood Glucose/analysis , C-Reactive Protein/analysis , Carotid Intima-Media Thickness/statistics & numerical data , Cross-Sectional Studies , Humans , Interleukin-6/blood , Lipids/blood , Logistic Models , Male , Plasminogen Activator Inhibitor 1/blood , Risk Factors , Tumor Necrosis Factor-alpha/blood , Vitamin D/analogs & derivatives , Vitamin D/bloodABSTRACT
INTRODUCTION: The fibrogenesis analysis in quimeric CCR1 and CCR5 mice revealed that CCR5 mediates its pro-fibrogenic effects in hepatic cells and promoting stellate cells. The blockage of co-receptors could preserve the progression of hepatic fibrosis in HIV/HCV co-infected patients. OBJECTIVE: To evaluate the beneficial effects on hepatic fibrosis in HIV/HCV co-infected patients that are on antiretroviral therapy (ART) with CCR5 co-receptor antagonists. METHOD AND MATERIALS: A multicentre, retrospective pilot study of the evaluation of hepatic fibrosis at mid- and long-term by non-invasive methods in a HIV/HCV co-infected patients cohort in the Valencian Community (Spain) that received ART with a CCR5 co-receptor antagonist. The cut-off points of serum marker tests of hepatic fibrosis were: AST to Platelet Ratio Index (APRI)<0.5 (F0-F1); >1.5 F2; >2 Cirrhosis and Forns Index<4.2 excludes fibrosis; >6.9>F2 fibrosis. Inclusion criteria was established for HIV/HCV co-infected patients on ART with CCR5 co-receptor antagonists that had no previous history of interferon and ribavirin treatment or those who were null-responders and received CCR5 co-receptor antagonist treatment in the previous year. Patients with HBV infection were excluded. RESULTS: A total of 71 male patients (69%) were reported. A CD4 nadir <100 cells/uL was observed in 42% of patients and 62% (44/71) had a basal CD4 level >350 cells/uL. According to genotypes, 50% were G-1a, 14% G-1b, 11% G-3 and 25% G-4. The median duration of treatment with Maraviroc (MVC) was the following: 45% took it over a year, 41% over two years and 14% over three years. Before starting treatment with MVC, we observed an initial fibrosis of F0-F1 in 49% of patients, F2-F3 in 24% and F4 in 27%. The medium follow-up was of 18.45 months. Progression to a higher fibrosis level was observed in five patients, 11 patients improved at least one stage and the others were stable over time. There were 38 patients taking MVC over two years, 27 patients in this group (59.38%) did not modify their fibrosis, 3 patients (11%) progressed and 8 (29.62%) showed regression of liver fibrosis in one stage. CONCLUSIONS: The data above shows a benefit over fibrosis progression with MVC, expressed by fibrosis serum marker tests in HIV/HCV co-infected patients with CCR5 tropism. The prolong treatment with MVC (over two years) has a better effect on liver fibrosis.
ABSTRACT
BACKGROUND: Decrease in HIV viral load (VL) is accompanied by decrease in microbial translocation (MT) and chronic inflammation, but the behavior of these markers in patients with HIV-VL <20 copies per milliliter is unknown. The aim of this study was to determine whether strict control of HIV-VL is associated with MT and chronic inflammation. METHODS: Observational cross-sectional study. INCLUSION CRITERIA: HIV patients receiving antiretroviral therapy and HIV-VL <200 copies per milliliter for more than 6 months. EXCLUSION CRITERIA: chronic liver disease, active infection, or antibiotic consumption. Recruitment: patients who consecutively visited the outpatient clinic in November 2011. Primary endpoint: molecular MT as determined by detection in plasma of 16S ribosomal DNA. Secondary variables: lipopolysaccharide, soluble CD14, tumor necrosis factor α, and interleukin 6. Primary explanatory variable: HIV-VL (COBAS AmpliPrep/COBAS TaqMan HIV-1 test, version 2.0) with a detection limit of 20 copies per milliliter. RESULTS: Fifty-two patients were included: 65% men, median age 45 years, HIV acquired predominantly through sex (75%), 40% Centers for Disease Control and Prevention stage C, and median CD4 lymphocyte count 552 cells per cubic millimeter (range, 126-1640 cells/mm). Molecular MT was observed in 46% and 18% of patients with low-level (20-200 copies/mL) and negative (<20 copies/mL) HIV-VL, respectively (P < 0.05). Plasma levels of inflammatory markers (tumor necrosis factor α and interleukin 6) were higher in patients with molecular MT (P < 0.01) and were not influenced for HIV-VL. CONCLUSIONS: Patients with HIV infection receiving treatment and negative HIV-VL (<20 copies/mL) present less frequently MT than patients with low-level HIV viremias (20-200 copies/mL). MT is associated with higher levels of inflammation markers, independent of HIV-VL.