Purpose
To develop recommendations for the management of acute hepatitis B by the Italian Society for the Study of Infectious and Tropical Diseases.
Methods
Development of the recommendations divided ...into three levels of evidence according to the GRADE system: A (high), B (medium) and C (low experts opinion), together with three recommendation levels: 1 (strong), 2 (medium), 3 (weak).
Results
The treatment with antivirals is in selected cases the mainstay of management of severe acute hepatitis, and should be started as a matter of urgency in order to prevent death.
Conclusions
These recommendations are meant to provide the rationale and practical indications for the management of acute hepatitis B (AHB).
A multicentre cross‐sectional survey was performed to provide an accurate picture of patients with chronic hepatitis B (CHB) cared for by Italian Infectious Diseases Centers (IDCs). This analysis ...describes factors associated with access to the treatment of CHB in a country where barriers to treatment are not expected to exist because of comprehensive coverage under the National Health System (NHS). The study was performed in 74 IDCs. The analysis focused on 3305 patients with CHB of 3760 HBsAg‐positive patients enrolled from March to September, 2008. To account for missing values, a Multiple Imputation method was used. Treatment was reported in 2091 (63.3%) patients. In the multivariate analysis, an increased chance of getting treatment was independently associated with 10 years increase of age at diagnosis (adjusted odds ratio aOR 1.2, 95% confidence interval CI 1.1–1.3, P < 0.001), HBeAg positivity (aOR 1.8, 95% CI 1.1–2.8, P < 0.001), cirrhosis (aOR 3.6, 95% CI 2–6.3, P = 0.012), HDV (aOR 1.6, 95% CI 1.02–2.5, P = 0.042) and HIV positivity (aOR 6.5, 95% CI 4–10.8, P < 0.001). Conversely, a decreased chance was associated with female gender (aOR 0.6, 95% CI 0.5–0.7, P < 0.001), immigration (aOR 0.6, 95% CI 0.5–0.9, P = 0.009), alcohol consumption (aOR 0.7, 95% CI 0.5–0.98, P = 0.04) and HCV positivity (aOR 0.5, 95% CI 0.3–0.8, P = 0.005). Our study shows that Italian IDCs treat a high percentage of patients with CHB. Nevertheless, disparities exist which are not related to the severity of disease limiting access to antiviral therapy of CHB, even in a country with a universal healthcare system.
Through this study we evaluated whether the HIV-1 tropism determined by genotypic analysis correlates with HIV-1 markers, such as CD4 cell count and plasma HIV-RNA. The analysis was performed on 1221 ...HIV-1 B-subtype infected patients with an available V3 sequence (all maraviroc naive). Of them, 532 were antiretroviral therapy (ART) naive and 689 ART experienced. Tropism determination was performed by using the geno2pheno (co-receptor) algorithm set at a false-positive rate (FPR) of 10% and 2%. Potential associations of FPR with CD4 cell count and viraemia were evaluated. Association of V3 mutations with genotypic-determined tropism was also evaluated according to different FPR ranges. About 26% of patients (either ART naive or ART experienced) were infected by X4-tropic viruses (using the classical 10% FPR cut-off). However, a significantly lower proportion of ART-naive patients had FPR ≤ 2% in comparison with ART-experienced patients (4.9% vs. 12.6%, respectively, p <0.001). The risk of advanced HIV-1 infection (with CD4 cell count ≤ 200 cells/mm3) was significantly greater in X4-infected patients, either ART-naive (OR (95% CI)), 4.2 (1.8–9.2); p 0.0006) or ART-experienced (2.3 (1.4–3.6); p 0.0003), with FPR set at 2% (but not at 10%). This finding was confirmed by multivariable logistic analysis. No relationship was found between viraemia and FPR ≤2%. Some X4-related mutations were significantly associated with FPR ≤2% (ART-naive patients, S11R, Y21V, G24K and G24R, p ≤0.001; ART-experienced patients, Y7K, S11R, H13Y, p ≤0.002). In conclusion, these findings show that within the context of genotypically-assessed CXCR4 tropism, FPR ≤2% defines (far better than 10%-FPR) a viral population associated with low CD4 rank, with potentially greater cytopathic effect, and with more advanced disease.
The combination of pegylated interferon (Peg‐IFN) and ribavirin is currently the gold standard therapy in patients with HCV chronic infection. The duration of therapy, as well as the therapeutic ...dosage, depend on the genotype. Identification of the genotype and rapid virological response (RVR) are widely accepted as the most important predictors of clinical outcome during antiviral therapy but to optimize cost‐benefits and to reduce possible side effects, further prognostic factors are needed. Squamous cell carcinoma antigens immunocomplex (SCCA‐IC) has been reported to be increased in the serum of patients with liver cancer. In this multicentric prospective study, we investigated the serum levels of SCCA‐IC in 103 patients with HCV chronic infection. Serum HCV‐RNA was detected before the beginning of treatment, after 4, 12, 24 or 48 weeks, and at week 24 during follow‐up. RVR, early virological response and sustained virological response (SVR) were assessed following the international guidelines. SCCA‐IC levels were higher in responders (238 AU, interquartile difference 130–556 AU) and decreased significantly to 125 AU (70–290 AU). The mean baseline value in nonresponders was 149 AU (86.5–306.5 AU), but after 4 weeks of treatment the serum levels decreased to 115 AU (80–280 AU): the profile of reduction was different between patients with or without a positive SVR. Logistic regression with SVR as dependent variable identified as significant independent variables: the reduction in SCCA‐IC after 1 month (OR = 4.82; 95% CI 1.39–16.67; P = 0.131) and a genotype other than 1 (OR = 0.094; 95% CI 0.21–0.42; P = 0.002); sex and age were also significant factors influencing SVR. SCCA‐IC seems to be a reliable independent prognostic marker of therapeutic effectiveness in anti‐HCV positive patients undergoing antiviral therapy.
Purpose
We have developed a sequencing assay for determining the usage of the genotypic HIV-1 co-receptor using peripheral blood mononuclear cell (PBMC) DNA in virologically suppressed HIV-1 infected ...patients. Our specific aims were to (1) evaluate the efficiency of V3 sequences in B versus non-B subtypes, (2) compare the efficiency of V3 sequences and tropism prediction using whole blood and PBMCs for DNA extraction, (3) compare the efficiency of V3 sequences and tropism prediction using a single versus a triplicate round of amplification.
Results
The overall rate of successful V3 sequences ranged from 100 % in samples with >3,000 copies HIV-1 DNA/10
6
PBMCs to 60 % in samples with <100 copies total HIV-1 DNA /10
6
PBMCs. Analysis of 143 paired PBMCs and whole-blood samples showed successful V3 sequences rates of 77.6 % for PBMCs and 83.9 % for whole blood. These rates are in agreement with the tropism prediction obtained using the geno2pheno co-receptor algorithm, namely, 92.1 % with a false-positive rate (FPR) of 10 or 20 % and of 96.5 % with an FPR of 5.75 %. The agreement between tropism prediction values using single versus triplicate amplification was 98.2 % (56/57) of patients using an FPR of 20 % and 92.9 % (53/57) using an FPR of 10 or 5.75 %. For 63.0 % (36/57) of patients, the FPR obtained via the single amplification procedure was superimposable to all three FPRs obtained by triplicate amplification.
Conclusions
Our results show the feasibility and consistency of genotypic testing on HIV-1 DNA tropism, supporting its possible use for selecting patients with suppressed plasma HIV-1 RNA as candidates for CCR5-antagonist treatment. The high agreement between tropism prediction by single and triple amplification does not support the use of triplicate amplification in clinical practice.
Background. Chronic cytomegalovirus (CMV) infection has been associated with immunosenescence and immunoactivation in the general population. In human immunodeficiency virus type 1 (HIV-1)-infected ...people, CMV coinfection, in addition to residual HIV replication and microbial translocation, has been proposed as a key factor in sustaining immune activation, even in individuals with a controlled HIV load. Methods. Patients from the ICONA Study with at least 1 CMV immunoglobulin G (IgG) test available without active CMV disease were included in the analysis. AIDS-defining event or AIDS-related death and severe non-AIDS-defining event or non-AIDS-related death were taken as clinical progression end points. Independent predictors of CMV were identified by multivariable logistic regression. Probabilities of reaching the end points were estimated by survival analyses. Results. A total of 6111 subjects were included, of whom 5119 (83.3%) were CMV IgG positive at baseline. Patients with CMV IgG positivity at baseline were more likely to develop a severe non-AIDS-defining event/non-AIDS-related death (adjusted hazard ratio HR, 1.53 95% confidence interval {CI}, 1.08-2.16. In particular, CMV seropositivity was an independent risk factor for cardiovascular and cerebrovascular diseases (adjusted HR, 2.27 95% CI, .97-5.32). Conclusions. In our study population, CMV/HIV coinfection was associated with the risk of severe non-AIDS-defining events/non-AIDS-related death, especially with cardiovascular and cerebrovascular events, independently of other prognostic factors. This finding supports a potential independent role of CMV coinfection in vascular/degenerative organ disorders in HIV-infected subjects.
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