Abstract
Objectives
Standard once-daily dosing of ceftriaxone may not lead to adequate antibiotic exposure in all cases of Staphylococcus aureus bacteraemia (SAB). Therefore, we compared clinical ...effectiveness of empirical antibiotic treatment with flucloxacillin, cefuroxime and ceftriaxone in adult patients with MSSA bacteraemia
Methods
We analysed data from the Improved Diagnostic Strategies in Staphylococcus aureus bacteraemia (IDISA) study, a multicentre prospective cohort study of adult patients with MSSA bacteraemia. Duration of bacteraemia and 30 day SAB-related mortality were compared between the three groups using multivariable mixed-effects Cox regression analyses.
Results
In total, 268 patients with MSSA bacteraemia were included in the analyses. Median duration of empirical antibiotic therapy was 3 (IQR 2–3) days in the total study population. Median duration of bacteraemia was 1.0 (IQR 1.0–3.0) day in the flucloxacillin, cefuroxime and ceftriaxone groups. In multivariable analyses, neither cefuroxime nor ceftriaxone were associated with increased duration of bacteraemia (respectively HR 1.08, 95% CI 0.73–1.60 and HR 1.22, 95% CI 0.88–1.71) compared with flucloxacillin, nor were the cephalosporins associated with higher 30 day SAB-related mortality (respectively, subdistribution HR (sHR) 1.37, 95% CI 0.42–4.52 and sHR 1.93, 95% CI 0.67–5.60).
Conclusions
In this study, we could not demonstrate a difference in duration of bacteraemia and 30 day SAB-related mortality between patients with SAB empirically treated with flucloxacillin, cefuroxime or ceftriaxone. Since sample size was limited, it is possible the study was underpowered to find a clinically relevant effect.
Background. The aim of this study was to investigate the association between immunodeficiency, viremia, and non—AIDS-defining malignancies (NADM). Methods. Patients starting combination ...antiretroviral therapy (cART) as of 1 January 1996 were selected from the AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort. In Cox models, risk factors for NADM were investigated. These included age, sex, transmission route, smoking, alcohol abuse, prior AIDS diagnosis, duration of exposure to cART, and estimated duration of human immunodeficiency virus infection. CD4+ cell count and viral load (VL) were considered as time-updated variables and as measures of cumulative exposure to CD4+ cell counts of <200, <350, or <500 cells/mm³ and detectable VL >50, >400, and >1000 copies/mL, respectively. Results. In a cohort of 11,459 patients, 236 NADMs were diagnosed; 102 were caused by infection, and 134 were attributable to other causes. Median CD4+ cell count at NADM diagnosis was 340 cells/mm³ (range, 210—540 cells/mm³). Median time to first NADM after starting cART was 5.0 years (range, 2.2-8.2 years). In multivariate models, cumulative exposure to CD4+ cell counts <200 cells/mm³ remained significant (hazard ratio HR, 1.12; range, 1.03-1.22) for each additional year of exposure. In stratified analyses, cumulative exposure to CD4+ cell counts <200 cells/mm³ was associated with malignancies possibly caused by infection (HR, 1.16; range, 1.03-1.31) but was not associated with other types of cancers. No significant effect of viremia was seen in either type of cancer. Conclusions. Cumulative exposure to CD4+ cell counts <200 cells/mm³ during cART was associated with an increased risk of infection-related non—AIDS-defining malignancies.
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BFBNIB, NUK, PNG, UL, UM, UPUK
Background The Netherlands has provided unrestricted access to direct-acting antivirals (DAAs) since November 2015. We analyzed the nationwide hepatitis C virus (HCV) treatment uptake among patients ...coinfected with human immunodeficiency virus (HIV) and HCV. Methods Data were obtained from the ATHENA HIV observational cohort in which >98% of HIV-infected patients ever registered since 1998 are included. Patients were included if they ever had 1 positive HCV RNA result, did not have spontaneous clearance, and were known to still be in care. Treatment uptake and outcome were assessed. When patients were treated more than once, data were included from only the most recent treatment episode. Data were updated until February 2017. In addition, each treatment center was queried in April 2017 for a data update on DAA treatment and achieved sustained virological response. Results Of 23574 HIV-infected patients ever linked to care, 1471 HCV-coinfected patients (69% men who have sex with men, 15% persons who formerly injected drugs, and 15% with another HIV transmission route) fulfilled the inclusion criteria. Of these, 87% (1284 of 1471) had ever initiated HCV treatment between 2000 and 2017, 76% (1124 of 1471) had their HCV infection cured; DAA treatment results were pending in 6% (92 of 1471). Among men who have sex with men, 83% (844 of 1022) had their HCV infection cured, and DAA treatment results were pending in 6% (66 of 1022). Overall, 187 patients had never initiated treatment, DAAs had failed in 14, and a pegylated interferon-alfa–based regimen had failed in 54. Conclusions Fifteen months after unrestricted DAA availability the majority of HIV/HCV-coinfected patients in the Netherlands have their HCV infection cured (76%) or are awaiting DAA treatment results (6%). This rapid treatment scale-up may contribute to future HCV elimination among these patients.
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Abstract Background Mortality among people with human immunodeficiency virus (HIV) declined with the introduction of combination antiretroviral therapy. We investigated trends in mortality in people ...with HIV from 1999 through 2020. Methods Data were collected from the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) cohort between January 1999 through January 2015 and the International Cohort Consortium of Infectious Disease (RESPOND) from October 2017 through December 2020. Age-standardized all-cause and cause-specific mortality rates, classified using Coding Causes of Death in HIV, were calculated. Poisson models were used to assess mortality over time. Results Among 55 716 participants followed for median 6 years (interquartile range, 3–11), 5263 died (mortality rate MR, 13.7/1000 person-years of follow-up PYFU; 95% confidence interval CI, 13.4–14.1). Changing mortality was observed: AIDS mortality was most common between 1999–2009 (n = 952; MR, 4.2/1000 PYFU; 95% CI, 4.0–4.5) and non-AIDS–defining malignancy (NADM) between 2010–2020 (n = 444; MR, 2.8/1000 PYFU; 95% CI, 2.5–3.1). In multivariable analysis, all-cause mortality declined (adjusted mortality rate ratio aMRR, 0.97 per year; 95% CI, .96–.98), mostly 1999–2010 (aMRR, 0.96 per year; 95% CI, .95–.97) but was stable 2011–2020 (aMRR, 1.00 per year; 95% CI, .96–1.05). Mortality due to all known causes except NADM also declined. Conclusions Mortality among people with HIV in the D:A:D and/or RESPOND cohorts declined between 1999–2009 and was stable over the period 2010–2020. This decline in mortality was not fully explained by improvements in immunologic–virologic status or other risk factors.
Background. Through 2 international traveler-focused surveillance networks (GeoSentinel and TropNet), we identified and investigated a large outbreak of acute muscular sarcocystosis (AMS), a rarely ...reported zoonosis caused by a protozoan parasite of the genus Sarcocystis, associated with travel to Tioman Island, Malaysia, during 2011–2012. Methods. Clinicians reporting patients with suspected AMS to GeoSentinel submitted demographic, clinical, itinerary, and exposure data. We defined a probable case as travel to Tioman Island after 1 March 2011, eosinophilia (>5%), clinical or laboratory-supported myositis, and negative trichinellosis serology. Case confirmation required histologic observation of sarcocysts or isolation of Sarcocystis species DNA from muscle biopsy. Results. Sixty-eight patients met the case definition (62 probable and 6 confirmed). All but 2 resided in Europe; all were tourists and traveled mostly during the summer months. The most frequent symptoms reported were myalgia (100%), fatigue (91%), fever (82%), headache (59%), and arthralgia (29%); onset clustered during 2 distinct periods: "early" during the second and "late" during the sixth week after departure from the island. Blood eosinophilia and elevated serum creatinine phosphokinase (CPK) levels were observed beginning during the fifth week after departure. Sarcocystis nesbitti DNA was recovered from 1 muscle biopsy. Conclusions. Clinicians evaluating travelers returning ill from Malaysia with myalgia, with or without fever, should consider AMS, noting the apparent biphasic aspect of the disease, the later onset of elevated CPK and eosinophilia, and
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Background. Guidelines for treatment of human immunodeficiency virus type 1 (HIV-1) infection consider lamivudine and emtricitabine to be interchangeable components in first-line combination ...antiretroviral therapy (cART). The evidence for their clinical equivalence in cART is inconsistent. The primary aim of this study was to evaluate the virological responses to lamivudine and emtricitabine in recommended cART. Methods. This was an observational study using data from the AIDS Therapy Evaluation in the Netherlands (ATHENA) nationwide HIV cohort. The virological responses to lamivudine and emtricitabine were compared by multivariable adjusted logistic regression and Cox proportional hazard models. Sensitivity analyses included propensity score-adjusted models. Results. Therapy-naive HIV-1–infected patients without baseline resistance (N = 4740) initiated lamivudine or emtricitabine with efavirenz/tenofovir or nevirapine/tenofovir. The use of lamivudine was associated with more virological failure at week 48 compared to emtricitabine with efavirenz/tenofovir (10.8% vs 3.6%; adjusted odds ratio AOR, 1.78; 95% confidence interval CI, 1.11–2.84) and nevirapine/tenofovir (27% vs 11%; AOR, 2.09; 95% CI, 1.25–3.52) in on-treatment analysis. Propensity score-adjusted models and intent-to-treat sensitivity analyses gave comparable results. The adjusted hazard ratio of virological failure at week 240 using lamivudine instead of emtricitabine was 2.35 (95% CI, 1.61–3.42) with efavirenz and 2.01 (95% CI, 1.36–2.98) with nevirapine. The inclusion of lamivudine or emtricitabine in cART did not influence the time to virological suppression within 48 weeks or the probability of virological rebound after successful virological suppression. Conclusions. The use of emtricitabine instead of lamivudine as part of cART was associated with better virological responses. These findings are relevant for settings with extensive use of lamivudine and for settings where generic lamivudine will be available.
Objectives
Direct‐acting antivirals (DAAs) for treatment of chronic hepatitis C virus (HCV) infection can cause drug–drug interactions (DDIs) with combination antiretroviral therapy (cART) and ...non‐cART co‐medication. We mapped how physicians manage DDIs between DAAs and co‐medication and analysed treatment outcomes.
Methods
Data were prospectively collected as part of the ATHENA HIV observational cohort and retrospectively analysed. Dutch patients with HIV/HCV coinfection who initiated treatment with DAAs between January 2015 and May 2016 were included. Co‐medication 3 months prior to and during DAA therapy was identified. Potential DDIs with the DAAs were checked using http://hep-druginteractions.org. DDIs were categorized as: (1) no interaction expected; (2) potential interaction; (3) contra‐indication; (4) no recommendation. These categories were used to determine which patients switched or had a DDI during DAA therapy with co‐medication.
Results
A total of 423 patients were treated with DAAs, of whom 418 (99%) used cART and 251 (59%) used non‐cART co‐medication. Before commencing DAA treatment, in 17 of 84 (20%) patients the non‐cART co‐medication which could result in a category 2/3 DDI was discontinued before DAA initiation, including two of six (33%) prescriptions of category 3 drugs. A total of 196 of 418 (47%) patients had a category 2/3 DDI between their DAA regimen and cART. Category 2/3 DDIs were prevented by switching cART in 78 of 147 (53%) and 47 of 49 (98%) patients. Overall, 367 of 423 (87%) patients have achieved a sustained virological response (33 in follow‐up).
Conclusions
Prescription patterns suggest that physicians are aware of potential DDIs between co‐medication and DAAs, in particular potential DDIs with cART. Greater awareness is needed concerning category 3 interactions between non‐cART co‐medication and DAAs.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Studies suggest that the HIV-1 epidemic in the Netherlands may have become more virulent, leading to faster disease progression if untreated. Analysis of CD4 cell count decline before antiretroviral ...therapy (ART) initiation, a surrogate marker for disease progression, may be hampered by informative censoring as ART initiation is more likely with a steeper CD4 cell count decline.
Development of CD4 cell count from 9 to 48 months after seroconversion was analyzed using a mixed-effects model and 2 models that jointly modeled CD4 cell counts and time to censoring event (start ART, <100 CD4 cells/mm³, or AIDS) among therapy-naïve MSM HIV-1 seroconverters in the Netherlands. These models make different assumptions about the censoring process.
All 3 models estimated lower median CD4 cell counts 9 months after seroconversion in later calendar years (623, 582, and 541 cells/mm³ for 1984-1995 n = 111, 1996-2002 n = 139, and 2003-2007 seroconverters n = 356, respectively, shared-parameter model). Only the 2 joint-models found a trend for a steeper decline of CD4 cell counts with seroconversion in later calendar years (overall p-values 0.002 and 0.06 for the pattern-mixture and the shared-parameter model, respectively). In the shared-parameter model the median decline from 9 to 48 months was 276 cellsmm³ for 1984-1995 seroconverters and 308 cells/mm³ for 2003-2007 seroconverters (difference in slope, p = 0.045).
Mixed-effects models underestimate the CD4 cell decline prior to starting ART. Joint-models suggest that CD4 cell count declines more rapidly in patients infected between 2003 and 2007 compared to patients infected before 1996.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
Lamivudine (3TC) and emtricitabine (FTC) are considered interchangeable in recommended tenofovir disoproxil‐fumarate (TDF)‐containing combination antiretroviral therapies (cARTs). This ...statement of equivalence has not been systematically studied. We compared the treatment responses to 3TC and FTC combined with TDF in boosted protease inhibitor (PI)‐based cART for HIV‐1‐infected patients.
Methods
An observational study in the AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort was carried out between 2002 and 2013. Virological failure rates, time to HIV RNA suppression < 400 copies/mL, and time to treatment failure were analysed using multivariable logistic regression and Cox proportional hazard models. Sensitivity analyses included propensity score‐adjusted models.
Results
A total of 1582 ART‐naïve HIV‐1‐infected patients initiated 3TC or FTC with TDF and ritonavir‐boosted darunavir (29.6%), atazanavir (41.5%), lopinavir (27.1%) or another PI (1.8%). Week 48 virological failure rates on 3TC and FTC were comparable (8.9% and 5.6%, respectively; P = 0.208). The multivariable adjusted odds ratio of virological failure when using 3TC instead of FTC with TDF in PI‐based cART was 0.75 95% confidence interval (CI) 0.32–1.79; P = 0.51. Propensity score‐adjusted models showed comparable results. The adjusted hazard ratio (HR) for treatment failure of 3TC compared with FTC was 1.15 (95% CI 0.58–2.27) within 240 weeks after cART initiation. The time to two consecutive HIV RNA measurements < 400 copies/mL within 48 weeks (HR 0.94; 95% CI 0.78–1.16) and the time to treatment failure after suppression < 400 copies/mL (HR 0.94; 95% CI 0.36–2.50) were not significantly influenced by the use of 3TC in TDF/PI‐containing cART.
Conclusions
The virological responses were not significantly different in treatment‐naïve HIV‐1‐infected patients starting either 3TC/TDF or FTC/TDF and a ritonavir‐boosted PI.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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