Definite Streptococcus bovis endocarditis: characteristics in 20 patients

ObjectiveTo determine the specific characteristics of Streptococcus bovis infective endocarditis (IE) by reviewing our own experience of S. bovis IE.MethodsTwenty episodes of definite S. bovis IE were reviewed in 20 patients hospitalized from 1980 to 1996.ResultsThe mean age was 62 ± 14 years, and 14 (70%) patients had no known predisposing cardiac condition. The principal antimicrobials used were penicillin G (N = 10) and amoxycillin (N = 8). Surgery was required in four (20%) patients. Neurologic complications occurred in eight (40%) patients, after initiation of therapy in six (75%) (mean time: 14 days). An unfavorable outcome was observed in four of 20 patients and tended to be more frequent in patients who had had neurologic complications (P – 0.10). Colonic tumors were present in 11 of 16 (69%) patients.ConclusionsAdvanced age, occurrence of IE on presumably normal valves, high rate of neurologic complications, associated gastrointestinal diseases and low mortality rate during initial follow-up are characteristic features of S. bovis IE observed in this study

Comparison of the Safety and Pharmacokinetics of ST-246® after IV Infusion or Oral Administration in Mice, Rabbits and Monkeys

ST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (IV) formulation may be required for some hospitalized patients who are unable to take oral medication. An IV formulation has been evaluated in three species previously used in evaluation of both efficacy and toxicology of the oral formulation. plasma concentrations. These effects were eliminated using slower IV infusions. associated toxicity. Shorter infusions at higher doses in NHP resulted in decreased clearance, suggesting saturated distribution or elimination. Elimination half-lives in all species were similar between oral and IV administration. The administration of ST-246 was well tolerated as a slow IV infusion

Pneumoproteins and biomarkers of inflammation and coagulation do not predict rapid lung function decline in people living with HIV

Chronic obstructive pulmonary disease (COPD) is among the leading causes of death worldwide and HIV is an independent risk factor for the development of COPD. However, the etiology of this increased risk and means to identify persons with HIV (PWH) at highest risk for COPD have remained elusive. Biomarkers may reveal etiologic pathways and allow better COPD risk stratification. We performed a matched case:control study of PWH in the Strategic Timing of Antiretoviral Treatment (START) pulmonary substudy. Cases had rapid lung function decline (> 40 mL/year FEV1 decline) and controls had stable lung function (+ 20 to − 20 mL/year). The analysis was performed in two distinct groups: (1) those who were virally suppressed for at least 6 months and (2) those with untreated HIV (from the START deferred treatment arm). We used linear mixed effects models to test the relationship between case:control status and blood concentrations of pneumoproteins (surfactant protein-D and club cell secretory protein), and biomarkers of inflammation (IL-6 and hsCRP) and coagulation (d-dimer and fibrinogen); concentrations were measured within ± 6 months of first included spirometry. We included an interaction with treatment group (untreated HIV vs viral suppression) to test if associations varied by treatment group. This analysis included 77 matched case:control pairs in the virally suppressed batch, and 42 matched case:control pairs in the untreated HIV batch (n = 238 total) who were followed for a median of 3 years. Median (IQR) CD4 + count was lowest in the controls with untreated HIV at 674 (580, 838). We found no significant associations between case:control status and pneumoprotein or biomarker concentrations in either virally suppressed or untreated PWH. In this cohort of relatively young, recently diagnosed PWH, concentrations of pneumoproteins and biomarkers of inflammation and coagulation were not associated with subsequent rapid lung function decline. Trial registration: NCT00867048 and NCT01797367

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Primary Staphylococcus aureus urinary tract infection: The role of undetected hematogenous seeding of the urinary tract

Staphylococcus aureus (SA) bacteriuria may accompany SA bacteremia, but primary SA urinary tract infection (UTI) may also occur. Our clinical observation of SA UTIs following intravenous catheter-related phlebitis lead us to review hematogenous and ascending route-related risk factors in patients with primary SA UTIs. The charts from all patients with SA UTIs over a 1.5-year period were reviewed for concurrent or recent hospitalization, intravenous catheterization, and for known UTI risk factors. Patients with concurrent SA bacteremia were excluded. Patients with Escherichia coli UTIs during the same period were included as controls. Twenty cases of primary SA UTI were compared with 43 E. coli UTI cases and they did not differ in age, diabetes mellitus, prostatic hypertrophy, previous UTI, or other urinary tract (UT) abnormality. However, cases were more likely than controls to have had recent or concurrent hospitalization, UT catheterization, and history of recent phlebitis. In multivariate analysis, UT catheterization and recent hospitalization retained significant association with SA UTI. Similar results were shown for the methicillin-resistant SA UTI subgroup. Even though UT catheterization is the main predisposing factor for primary SA UTI, some cases may be mediated through unrecognized preceding bacteremia related to intravascular device exposure or other healthcare-related factors. © 2010 Springer-Verlag

Expanded postexposure prophylaxis for simultaneous multiple source HIV exposure in a health-care worker

We report an extreme case of high-grade needlestick exposure of a health-care worker to serum from multiple HIV-infected patients after trying to prematurely remove the respective tubes from an automated biochemical analyser. After review of the medical records of the eight source patients, we offered the health-care worker an expanded postexposure prophylaxis regimen including the entry inhibitor enfuvirtide. She refused to take subcutaneous injections, so we recommended the use of the integrase inhibitor raltegravir. She completed therapy without problems and periodic evaluation for HIV transmission up to nine months after the incident was negative

First-time use of bevacizumab for metastatic hepatocellular carcinoma in a HIV/HBV coinfected patient. A case report

A case of a HIV-1 infected patient with history of chronic hepatitis B and chronic alcohol use without cirrhosis, who presented with aggressive hepatocellular carcinoma (HCC) with multiple metastasis is presented. Systemic chemotherapy combined with use of bevacizumab (anti-VEGF monoclonal antibody) was without effect and the patient succumbed to his disease within weeks. Relatively recent data indicate that HCC may be extremely aggressive in HIV/HBV or HIV/HCV coinfected patients with younger age at presentation, shorter evolution time, a more advanced stage at presentation with higher rates of extrahepatic-extranodal metastases and, finally, a reduced survival rate as compared with HIV-negative patients. To our knowledge, this is the first report in the English literature of bevacizumab use for metastatic hepatocellular carcinoma in HIV infected patients

HIV continuum of care: Bridging cross-sectional and longitudinal analyses

Objective: The aim of this study was to propose a unified continuum-of-care (CoC) analysis combining cross-sectional and longitudinal elements, incorporating time spent between stages. Design: The established 90-90-90 target follows a cross-sectional four-stage CoC analysis, lacking information on timing of diagnosis, antiretroviral therapy (ART) initiation, and viral suppression durability. Methods: Data were derived from the Athens Multicenter AIDS Cohort Study (AMACS). In the cross-sectional CoC, we added stratification of diagnosed people with HIV (PWH) by estimated time from infection to diagnosis; of those who ever initiated ART or achieved viral suppression by corresponding current status (in 2018); and cumulative incidence function (CIF) of ART initiation and viral suppression, treating loss-to-followup (LTFU) as competing event. Viral suppression was defined as viral load less than 500 copies/ml. Viral suppression durability was assessed by the CIF of viral load rebound. Findings: About 89.1% of PWH in 2018 were diagnosed (range of diagnoses: 1980 - 2018). Median time to diagnosis was 3.5 years (IQR: 1.1 - 7.0). Among diagnosed, 89.1% were ever treated, of whom 86.7% remained on ART. CIF of ART initiation and LTFU before ART initiation were 80.9 and 6.0% at 5 years since diagnosis, respectively. Among treated, 89.4% achieved viral suppression, of whom 87.4% were currently virally suppressed. The CIF of viral load rebound was 24.2% at 5 years since first viral suppression but substantially reduced in more recent years. Interpretation: The proposed analysis highlights time gaps in CoC not evident by the standard cross-sectional approach. Our analysis highlights the need for early diagnosis and identifies late presenters as a key population for interventions that could decrease gaps in the CoC. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved