293 research outputs found
The treatment of chronic hepatitis C virus infection in HIV co-infection
Chronic HCV co-infection is present in up to one third of HIV-positive patients in Europe. In recent years, apart from the traditional transmission route of intravenous drug abuse, outbreaks of sexually transmitted acute HCV infections, mainly among HIV-positive men who have sex with men, have contributed to the overall disease burden
a meta-analysis and historical comparison
Background About one third of patients infected with human immunodeficiency
virus (HIV) also have chronic hepatitis due to hepatitis C virus (HCV). HCV
therapy with simeprevir, pegylated interferon alfa (PegIFNα) and ribavirin
(RBV) have been shown to be superior to PegIFNα + RBV alone in non-HIV
patients, but no randomized trials in patients with HCV genotype 1 (HCV-1) /
HIV coinfection are available. Methods This was a historical comparison of
study C212 (simeprevir + PegIFNα-2a + RBV in patients with HCV-1/HIV
coinfection) with studies in which HCV-1/HIV coinfected patients were treated
with PegIFNα-2a + RBV alone. A systematic literature search was performed to
identify eligible studies. Efficacy and safety results of PegIFNα-2a + RBV
studies were combined in random- and fixed-effects inverse-variance weighted
meta-analyses of proportions using the Freeman-Tukey double arcsin
transformation method, and compared with the results of study C212. Results
The literature search revealed a total of 2392 records, with 206 articles
selected for full-text review. Finally, 11 relevant articles reporting on 12
relevant study groups were included. Results on sustained virologic response
24 weeks after end of treatment (SVR24) were available from all 12 study
groups. Pooled SVR24 for PegIFNα-2a + RBV from the random-effects meta-
analysis was 28.2 % (95 % CI 23.8 % to 32.9 %). The comparison between study
C212 (SVR24 = 72.6 %; 95 % CI 63.1 % to 80.9 %) revealed substantial
superiority of simeprevir + PegIFNα-2a + RBV compared to PegIFNα-2a + RBV
alone, with an absolute risk difference of 45 % (95 % CI 34 to 55). This
finding was robust in a sensitivity analysis that only included historical
studies with a planned treatment duration of at least 48 weeks and the same
RBV dose as in study C212. No increases in the frequency of important adverse
event categories including anemia were identified, but these analyses were
limited by the low number of studies. Conclusion This historical comparison
provides first systematic evidence for the superiority of simeprevir +
PegIFNα-2a + RBV compared to PegIFNα-2a + RBV in patients with HCV-1 / HIV
coinfection. Given the limitations of the historical comparison for safety
endpoints, additional data on the comparative safety of simeprevir in patients
with HCV-1 / HIV coinfection would be desirable. Trial registration Identifier
for study TMC435-TiDP16-C212 (ClinicalTrials.gov): NCT01479868
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
Simeprevir with pegylated interferon alfa 2a plus ribavirin for treatment of hepatitis C virus genotype 1 in patients with HIV: a meta-analysis and historical comparison
Additional data on meta-analyses and historical comparisons. (DOCX 18 kb
Latent infection of human bocavirus accompanied by flare of chronic cough, fatigue and episodes of viral replication in an immunocompetent adult patient, cologne, Germany
Publisher Copyright: © 2016 The Authors.Introduction: The human bocavirus (HBoV) is a parvovirus and is associated with mild to lifethreatening acute or persisting respiratory infections, frequently accompanied by further pathogens. So far, there is limited knowledge on the mechanisms of persistence, and no reports on chronic infections or latency have been published so far. Case presentation: An immunocompetent male patient suffers from a chronic HBoV1 infection, i.e. viral DNA was detected in both serum and bronchoalveolar lavage (BAL) for >5 months without co-infections and with respiratory symptoms resolved spontaneously while receiving symptomatic treatment with montelukast and corticosteroids. Following the symptomatic medication of a chronic infection with HBoV1 viraemia indicating active viral replication lasting over 5 months, the patient cleared the viraemia and no further viral DNA was detectable in the BAL. However, by fluorescence in situ hybridization analyses of mucosal biopsies, it was shown that the virus genome still persisted in the absence of viral shedding but in a more compact manner possibly representing a supercoiled episomal form of this otherwise linear singlestranded DNA genome. This indicated the entry into a latency phase. Moreover, the cytokine profile and the IP-10/TARC ratio, a marker for fibrotization, seem to have been altered by HBoV1 replication. Although specific IgG antibodies were detectable during the whole observation period, they showed an apparently insufficient neutralising activity. Conclusion: On the one hand, these findings suggest that the symptomatic medication may have led to clearance of the virus from blood and airways and, moreover, that the viral DNA persists in the tissue as an altered episomal form favoured by lacking neutralising antibodies. This appears to be important in order to reduce possible long-term effects such as lung fibrosis.publishersversionPeer reviewe
Selection and counterselection of the rtI233V adefovir resistance mutation during antiviral therapy
Recently, we reported on three patients with chronic hepatitis B virus (HBV) infection for whom adefovir (ADF) therapy virologically failed, most likely due to a preexisting rtI233V HBV polymerase mutation. Here, we describe two further patients with chronic HBV infection who were found to develop the rtI233V mutation after initiation of ADF therapy. These patients represent the first cases known so far in which the rtI233V ADF resistance mutation evolved under persistent HBV replication during HBV therapy with ADF. Interestingly, one of the previously described patients, who was initially successfully switched from ADF to tenofovir (TDF) and became virologically suppressed subsequently, experienced a moderate but remarkable rebound of HBV viremia after switching from TDF to entecavir, due to the emergence of renal toxicity. Thus, we provide evidence for the selection and counterselection of the rtI233V ADF resistance mutation during antiviral therapy
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