Hyaluronic acid levels predict risk of hepatic encephalopathy and liver-related death in HIV/viral hepatitis coinfected patients

Background: Whereas it is well established that various soluble biomarkers can predict level of liver fibrosis, their ability to predict liver-related clinical outcomes is less clearly established, in particular among HIV/viral hepatitis co-infected persons. We investigated plasma hyaluronic acid’s (HA) ability to predict risk of liver-related events (LRE; hepatic coma or liver-related death) in the EuroSIDA study. Methods: Patients included were positive for anti-HCV and/or HBsAg with at least one available plasma sample. The earliest collected plasma sample was tested for HA (normal range 0–75 ng/mL) and levels were associated with risk of LRE. Change in HA per year of follow-up was estimated after measuring HA levels in latest sample before the LRE for those experiencing this outcome (cases) and in a random selection of one sixth of the remaining patients (controls). Results: During a median of 8.2 years of follow-up, 84/1252 (6.7%) patients developed a LRE. Baseline median (IQR) HA in those without and with a LRE was 31.8 (17.2–62.6) and 221.6 ng/mL (74.9–611.3), respectively (p<0.0001). After adjustment, HA levels predicted risk of contracting a LRE; incidence rate ratios for HA levels 75–250 or ≥250 vs. <75 ng/mL were 5.22 (95% CI 2.86–9.26, p<0.0007) and 28.22 (95% CI 14.95–46.00, p<0.0001), respectively. Median HA levels increased substantially prior to developing a LRE (107.6 ng/mL, IQR 0.8 to 251.1), but remained stable for controls (1.0 ng/mL, IQR –5.1 to 8.2), (p<0.0001 comparing cases and controls), and greater increases predicted risk of a LRE in adjusted models (p<0.001). Conclusions: An elevated level of plasma HA, particularly if the level further increases over time, substantially increases the risk of contracting LRE over the next five years. HA is an inexpensive, standardized and non-invasive supplement to other methods aimed at identifying HIV/viral hepatitis co-infected patients at risk of hepatic complications

Regional differences in AIDS and non-AIDS related mortality in HIV-positive individuals across Europe and Argentina: the EuroSIDA study

BACKGROUND Differences in access to care and treatment have been reported in Eastern Europe, a region with one of the fastest growing HIV epidemics, compared to the rest of Europe. This analysis aimed to establish whether there are regional differences in the mortality rate of HIV-positive individuals across Europe, and Argentina. METHODS 13,310 individuals under follow-up were included in the analysis. Poisson regression investigated factors associated with the risk of death. FINDINGS During 82,212 person years of follow-up (PYFU) 1,147 individuals died (mortality rate 14.0 per 1,000 PYFU (95% confidence interval [CI] 13.1-14.8). Significant differences between regions were seen in the rate of all-cause, AIDS and non-AIDS related mortality (global p<0.0001 for all three endpoints). Compared to South Europe, after adjusting for baseline demographics, laboratory measurements and treatment, a higher rate of AIDS related mortality was observed in East Europe (IRR 2.90, 95%CI 1.97-4.28, p<.0001), and a higher rate of non-AIDS related mortality in North Europe (IRR 1.51, 95%CI 1.24-1.82, p<.0001). The differences observed in North Europe decreased over calendar-time, in 2009-2011, the higher rate of non-AIDS related mortality was no longer significantly different to South Europe (IRR 1.07, 95%CI 0.66-1.75, p = 0.77). However, in 2009-2011, there remained a higher rate of AIDS-related mortality (IRR 2.41, 95%CI 1.11-5.25, p = 0.02) in East Europe compared to South Europe in adjusted analysis. INTERPRETATIONS There are significant differences in the rate of all-cause mortality among HIV-positive individuals across different regions of Europe and Argentina. Individuals in Eastern Europe had an increased risk of mortality from AIDS related causes and individuals in North Europe had the highest rate of non-AIDS related mortality. These findings are important for understanding and reviewing HIV treatment strategies and policies across the European region

Factors Associated with the Development of Opportunistic Infections in HIV-1-Infected Adults with High CD4+ Cell Counts: A EuroSIDA Study

BackgroundLimited data exist on factors predicting the development of opportunistic infections (OIs) at higher-than-expected CD4+ cell counts in human immunodeficiency virus (HIV) type 1-infected adults MethodsMultivariate Poisson regression models were used to determine factors related to the development of groups of OIs above their respective traditional upper CD4+ cell count thresholds: group 1 (⩾100 cells/μL), OIs caused by cytomegalovirus, Mycobacterium avium complex, and Toxoplasma gondii; group 2 (⩾200 cells/μL), Pneumocystis pneumonia and esophageal candidiasis; and group 3 (⩾300 cells/μL), pulmonary and extrapulmonary tuberculosis ResultsIn groups 1, 2, and 3, 71 of 9219, 125 of 7934, and 36 of 7838 patients, respectively, developed ⩾1 intragroup OI. The strongest predictor of an OI in groups 1 and 2 was current CD4+ cell count (for group 1, incidence rate ratio [IRR] per 50% lower CD4+ cell count, 5.37 [95% confidence interval {CI}, 3.71-7.77]; for group 2, 4.28 [95% CI, 2.98-6.14]). Injection drug use but not current CD4+ cell count predicted risk in group 3. Use of antiretroviral treatment was associated with a lower incidence of OIs in all groups, likely by reducing HIV-1 RNA levels (IRR per 1-log10 copies/mL higher HIV-1 RNA levels for group 1, 1.50 [95% CI, 1.15-1.95]; for group 2, 1.68 [95% CI, 1.40-2.02]; and for group 3, 1.89 [95% CI, 1.40-2.54]) ConclusionAlthough the absolute incidence is low, the current CD4+ cell count and HIV-1 RNA level are strong predictors of most OIs in patients with high CD4+ cell count

Influence of Hepatitis C Virus Infection on HIV-1 Disease Progression and Response to Highly Active Antiretroviral Therapy

ObjectiveTo assess hepatitis C virus (HCV) antibody prevalence in the EuroSIDA cohort, along with survival, human immunodeficiency virus (HIV)-1 disease progression, virologic response (plasma HIV-1 RNA load of <500 copies/mL), and CD4 cell count recovery by HCV serostatus in patients initiating highly active antiretroviral therapy (HAART) ResultsHCV serostatus at or before enrollment was available for 5957 patients; 1960 (33%) and 3997 (67%) were HCV seropositive and seronegative, respectively. No association between an increased incidence of acquired immunodeficiency syndrome-defining illnesses or death and HCV serostatus was seen after adjustment for other prognostic risk factors known at baseline (adjusted incidence rate ratio [IRR], 0.97 [95% confidence interval {CI}, 0.81-1.16]). However, there was a large increase in the incidence of liver disease-related deaths in HCV-seropositive patients in adjusted models (IRR, 11.71 [95% CI, 6.42-21.34]). Among 2260 patients of known HCV serostatus initiating HAART, after adjustment, there was no significant difference between HCV-seropositive and -seronegative patients with respect to virologic response (relative hazard [RH], 1.13 [95% CI, 0.84-1.51]) and immunologic response, whether measured as a ⩾50% increase (RH, 0.94 [95% CI, 0.77-1.16]) or a ⩾50 cells/μL increase (RH, 0.92 [95% CI, 0.77-1.11]) in CD4 cell count after HAART initiation ConclusionsHCV serostatus did not affect the risk of HIV-1 disease progression, but the risk of liver disease-related deaths was markedly increased in HCV-seropositive patients. The overall virologic and immunologic responses to HAART were not affected by HCV serostatu

Association of Virus Load, CD4 Cell Count, and Treatment with Clinical Progression in Human Immunodeficiency Virus-Infected Patients with Very Low CD4 Cell Counts

This study prospectively assessed the impact of treatment modality, virus load, and CD4 cell count of <50 cells/mm3 on human immunodeficiency virus disease progression. The incidence rate of new AIDS disease or death was 54.8 (95% confidence interval, 48.7-59.9) per 100 person-years of follow-up. Independent predictors related to progression were latest CD4 cell count (relative risk [RR], 0.84/10 mm3 higher; P<.0001), latest hemoglobin level (RR, 0.79/g/L higher; P<.0001), Pneumocystis carinii pneumonia prophylaxis (RR, 0.49; P<.0001), latest body mass index (RR, 0.93/kg/m2 higher; P=.002), latest virus load (RR, 1.11/log10 higher; P=.03), and intensity of treatment (RR, 1.82, P=.004; RR 2.27, P<.0001; RR 2.46, P=.0001; RR 2.33 P<.0006; 5.10, P<.0001, respectively, for 4, 3, 2, 1, or no drugs vs. ⩾5 drugs). Although reverse causality cannot be excluded, more intense antiviral treatment appears to decrease the risk of progression in immunocompromised patient

O331 Patterns of viral suppression on cART as predictors of uncontrolled viremia after starting a new antiretroviral after 1 January 2003

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Increased incidence rates of positive blood cultures shortly after chemotherapy compared to radiotherapy among individuals treated for solid malignant tumours

BACKGROUND: Cancer treatments suppress immune function and are associated with increased risk of infections, but the overall burden of serious infectious diseases in treated patients has not been clearly elucidated. METHODS: All patients treated for solid malignant tumours with radiotherapy (RT) and/or standard first-line chemotherapy (C) at the Department of Oncology at Rigshospitalet between 01/1/2010 and 31/12/2016 were included. Patients were followed from treatment initiation until the first of new cancer treatment, 1 year after treatment initiation, end of follow-up or death. Incidence rates (IR) of positive blood culture (PBC) per 1000 person-years follow-up (PYFU) were calculated. FINDINGS: 12,433 individuals were included, 3582 (29%), 6349 (51%), and 2502 (20%) treated with RT, C, or both RT & C, respectively, contributing 8182 PYFU. 429 (3%) individuals experienced 502 unique episodes of PBC, incidence rate (95% CI) 52.43 (47.7, 57.6) per 1000 PYFU. The 30-day mortality rate after PBC was 24% independent of treatment modality. Adjusted incidence rate ratios in the first 3 months (95% CI) after PBC significantly varied by treatment: 2.89 (1.83, 4.55) and 2.52 (1.53, 4.14) for C and RT & C compared to RT. Escherichia coli (n = 127, 25%) was the top microorganism identified. INTERPRETATION: PBCs are not common, but when they occur, mortality is high

A Clinically Prognostic Scoring System for Patients Receiving Highly Active Antiretroviral Therapy: Results from the EuroSIDA Study

The risk of clinical progression for human immunodeficiency virus (HIV)-infected persons receiving treatment with highly active antiretroviral therapy (HAART) is poorly defined. From an inception cohort of 8457 HIV-infected persons, 2027 patients who started HAART during prospective follow-up were examined. Results were validated in another 2 groups of patients (n=1946 and n=1442). In total, 200 patients (9.9%) experienced clinical progression during 5177 person-years (incidence, 3.9/100 years). The most recently measured CD4 cell count, virus load, and hemoglobin level all were independently related to the risk of clinical progression, as was a diagnosis of severe AIDS before the start of HAART. On the basis of these findings, a scoring system was derived (range, 0-17). A single unit increase in the score was associated with a 38% increased risk of clinical progression (relative hazard, 1.38; 95% confidence interval, 1.33-1.43; P<.0001). The scoring system was validated with remarkably good agreement in the 2 other cohorts. This system can be used in patient and resource managemen

Long-term trends of alanine aminotransferase levels among persons living with human immunodeficiency virus/hepatitis B virus with and without hepatitis delta coinfection.

Background Hepatitis delta virus (HDV) infection accelerates the progression of liver disease in persons living with HIV and hepatitis B virus (HBV) coinfection. We explored the association between HDV infection and alanine aminotransferase (ALT) elevation during tenofovir-containing antiretroviral treatment among persons living with HIV/HBV. Materials and methods We included persons living with HIV/HBV with and without HDV starting tenofovir-containing antiretroviral therapy (ART) in three European cohorts with at least 18 months of follow-up. We defined HDV infection as a positive anti-HDV antibody test. We assessed risk factors for ALT elevation ≥ 1.25x upper limit of normal after 5 years of tenofovir-treatment using multivariate logistic regression models. The difference in ALT trends between individuals with and without HDV was evaluated using linear mixed effects models. Results 61/518 (11.8%) participants had an HDV infection. Among individuals with HDV, 63.9% had ALT elevation after 2 years and 55.6% after 5 years of tenofovir, whereas the estimates were 34.1% after two and 27.0% after 5 years in those without HDV. HDV coinfection (adjusted odds ratio 2.8, 95% confidence interval 1.4-5.8) and obesity at baseline (adjusted odds ratio 3.2, 95% confidence interval 1.2-8.0) were associated with ALT elevation after 5 years of tenofovir therapy. Mean ALT levels were consistently higher during follow-up in participants with HDV compared to those without HDV. Conclusion Persistent ALT elevation is common in persons living with HIV/HBV in Europe despite adequate HBV therapy. HDV coinfection and obesity are independent risk factors for persistent ALT elevation during long-term tenofovir treatment