RESUMO
OBJECTIVE: To investigate Corynebacterium striatum as a nosocomial pathogen infecting hard-to-heal peripheral wounds, such as skin wounds, soft tissue abscesses and osteomyelitis. As of 2023, the medical community were alerted against the risk of emerging systemic and central infections; on the other hand literature on peripheral cutaneous regions is still scarce. METHOD: In this study, two groups of patients with similar lesions which were infected were compared: one group with the presence of the coryneform rod, the other without. RESULTS: In total, Corynebacterium striatum was cultured from 62 patients and 131 samples. Corynebacterium striatum infection correlated well with the presence of: foot ulcer; venous leg ulcer; altered ambulation and/or altered foot loading; peripheral vascular and arterial disease; hospitalisation; malignancy; spinal cord injury; and recent administration of antibiotics (p<0.05 for all associations). Patients with Corynebacterium striatum had a lower overall survival rate compared to patients in the non-Corynebacterium striatum group (28.6 versus 31.6 months, respectively; p=0.0285). Multivariate analysis revealed that Corynebacterium striatum infection was an independent factor for poor prognosis (p<0.0001). CONCLUSION: In view of the findings of our study, Corynebacterium striatum appears to be an important opportunistic pathogen infecting peripheral tissues and complicating wound healing. Given its numerous and worrying virulence factors (such as multidrug resistance and biofilm production), particular attention should be given to this pathogen by professional wound care providers in nosocomial and outpatient environments.
Assuntos
Infecções por Corynebacterium , Infecção Hospitalar , Humanos , Estudos Prospectivos , Corynebacterium , Infecções por Corynebacterium/microbiologia , Cicatrização , Infecção Hospitalar/microbiologiaRESUMO
Antiviral therapy has revolutionized treatment of chronic HBV infections. First generation compounds, lamivudine and adefovir, displayed a high rate of treatment failures, and have been replaced by more potent compounds with high genetic barrier to resistance. However, the evolution of the virus towards resistance due the use of first generation compounds may still provide useful information for a better management of current antivirals. A single center sequence database including 705 HBV reverse transcriptase sequences from patients failing antiviral treatments (2002-2012) has been statistically analyzed to highlight viral evolution in relationship to the use of antiviral compounds and to their associations/sequencing in those years. The influence of viral genotypes and polymorphisms on resistance-related mutational patterns was also investigated. This study documents how, after the first years of antiviral therapy, the use of adefovir as an add-on strategy allowed a consistent reduction treatment failures. It also documents the effects of the initial misuse of entecavir in lamivudine experienced patients. In the latest years, the correct use of entecavir and the introduction of tenofovir allowed further curbing of resistance-related treatment failures, which virtually disappeared. Furthermore, the study allows a better understanding of how viral genotype (A vs D) conditions specific mutational pathways to resistance against lamivudine and entecavir, and demonstrates that the use of adefovir in lamivudine experienced patients is associated to peculiar mutational patterns, in particular A181V + F/Y221L. Despite some concern may arise for patients previously treated with lamivudine/adefovir, in sequence or combination, where the virus may have developed a lower genetic barrier against resistance to tenofovir, the outlook of antiviral treatment of HBV infection should be quite optimistic.
Assuntos
Adenina/análogos & derivados , Farmacorresistência Viral/genética , Vírus da Hepatite B/enzimologia , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Mutação , Organofosfonatos/uso terapêutico , DNA Polimerase Dirigida por RNA/genética , Adenina/uso terapêutico , Antivirais/administração & dosagem , Antivirais/farmacologia , Antivirais/uso terapêutico , Análise Mutacional de DNA , DNA Viral/genética , Quimioterapia Combinada , Evolução Molecular , Genótipo , Guanina/análogos & derivados , Guanina/uso terapêutico , Hepatite B Crônica/virologia , Humanos , Polimorfismo Genético , DNA Polimerase Dirigida por RNA/efeitos dos fármacos , Análise de Sequência , Tenofovir/uso terapêutico , Falha de TratamentoRESUMO
BACKGROUND: Entecavir is the drug of choice as first-line treatment for treatment-naive HBV patients. As a result of the high genetic barrier to resistance, treatment failure remains rare, but occurs within 3 years of initiation, suggesting that viral genetic characteristics may provide a fast lane to resistance. One of the main concerns is the long time to viral suppression observed in some (even treatment-naive) patients. The reasons for this phenomenon were investigated in a group of chronic hepatitis B treatment-naive patients. METHODS: Out of 23 treatment-naive patients starting entecavir, the 5 with the best and those with the worst viral load decay curves were selected for the study. Quasispecies analysis was performed for the reverse transcriptase/hepatitis B surface antigen (HBsAg) open reading frame (ORF) by ultra-deep pyrosequencing. For each patient, the analysis was performed at baseline (T0) and when viraemia reached between 15,000 and 200 IU/ml (T1). RESULTS: The few resistance mutations present at T0 were not selected by treatment; no other resistance mutations or suggestive mutational patterns were selected at T1. Selective pressure analysis indicated that both at T0 and T1 the HBsAg ORF was subjected to a significantly higher pressure in rapid responders, especially in a region rich in cytotoxic T-lymphocyte (CTL) epitopes. CONCLUSIONS: The results did not provide evidence that a slower response to entecavir is due to the emergence of less sensitive variants. Rather, the lower selective pressure and variability in humoral and CTL epitopes in slow responders suggests that their immune response might be at odds in rapidly clearing infected cells from the liver.
Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Genótipo , Guanina/uso terapêutico , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Humanos , Pessoa de Meia-Idade , Filogenia , Carga ViralRESUMO
HCV quasispecies variability represents the background for the selection of mutations and for the development of drug resistance. Natural aminoacid changes in NS3, associated with reduced protease inhibitor susceptibility, have been observed in treatment-naïve patients. Massively parallel sequencing has been used to analyze NS3 quasispecies in patients infected with HCV genotype 1, naive to anti-HCV treatment, with/without HIV-coinfection, to establish the genetic heterogeneity and the presence of amino acid substitutions at positions responsible for drug resistance. Genomes carrying substitutions represented either predominant or minority components of viral quasispecies, and were observed in 85.7% of patients. Multiple substitutions, frequently associated on the same haplotype, were observed in 46.4% of patients. High resistance combinations were not detected, neither on the same genome, nor in the whole quasispecies. Heterogeneity of HCV NS3 was lower in HIV-coinfected as compared to HCV-monoinfected patients, but factors underlying this difference remain to be established. Although the relevance of naturally occurring mutations with respect of resistance development and probability of success of direct acting antivirals is questioned, UDPS may be beneficial to help understanding viral dynamics, providing high resolution view of viral diversity.
Assuntos
Coinfecção/virologia , Infecções por HIV/virologia , Hepacivirus/enzimologia , Hepatite C/virologia , Mutação de Sentido Incorreto , Proteínas não Estruturais Virais/genética , Adulto , Idoso , Farmacorresistência Viral , Feminino , Variação Genética , HIV-1/fisiologia , Hepacivirus/classificação , Hepacivirus/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas não Estruturais Virais/metabolismoRESUMO
INTRODUCTION: In western countries the transmission of hepatitis B virus (HBV) transmission through multi-patients lancing devices has been inferred since early '90s, however no study has ever provided biological evidence which directly link these device with HBV cross-infection. Here we present results of an outbreak investigation which could associate, by molecular techniques, the use of lancing device on multiple patients with HBV transmission in an Italian oncohematology unit. METHODS: The outbreak investigation was designed as a retrospective cohort study to identify all potential cases. All cases identified were eventually confirmed through molecular epidemiology techniques. Audit of personnel including extensive review of infection control measures and reviewing personnel's tests for HBV was done identify transmission route. RESULTS: Between 4 May 2006 and 21 February 2007, six incident cases of HBV infection were reported among 162 patients admitted in the oncohematology. The subsequent molecular instigation proved that 3 out 6 incident cases and one prevalent cases (already infected with HBV at the admission) represented a monophyletic cluster of infection. The eventual environmental investigation found that an identical HBV viral strain was present on a multi-patients lancing device in use in the unit and the inferential analysis showed a statistically significant association between undergoing lancing procedures and the infection. DISCUSSION: This investigation provide molecular evidence to link a HBV infection cluster to multi-patients lancing device and highlights that patients undergoing capillary blood sampling by non-disposable lancing device may face an unacceptable increased risk of HBV infection. Therefore we believe that multi-patients lancing devices should be banned from healthcare settings and replace with disposable safety lancets that permanently retract to prevent the use of the same device on multiple patients. The use of non-disposable lancing devices should be restricted to individual use at patients' home.
Assuntos
Infecção Hospitalar/epidemiologia , Infecção Hospitalar/transmissão , Surtos de Doenças , Hepatite B/epidemiologia , Hepatite B/transmissão , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Humanos , Masculino , Pessoa de Meia-Idade , FilogeniaAssuntos
Antivirais/farmacologia , HIV/genética , Vírus da Hepatite B/genética , Mutação , DNA Viral/genética , Farmacorresistência Viral , HIV/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Hepatite B/tratamento farmacológico , Hepatite B/virologia , Vírus da Hepatite B/efeitos dos fármacos , HumanosRESUMO
A retrospective review was performed comparing lamivudine-resistance mutation patterns between patients infected with hepatitis B virus (HBV) with or without human immunodeficiency virus (HIV) co-infection. Medical records that included a genotypic test of patients infected with HBV and treated with lamivudine as the only anti-HBV drug were reviewed. Pol gene mutations were assessed by direct sequencing of the reverse transcriptase fragment 125-213 aa. Eighty-nine patients infected with HBV (29 co-infected with HIV) with rtM204V or rtM204I mutations were included. Multiple mutations associated with the YMDD motif were observed in 33 (55%) of 60 patients infected with HBV only and in 28 (96.6%) of patients co-infected with HIV/HBV. In this latter group, the prevalence of the rtV173L + rtL180M + rtM204V triple mutation was 31% versus a prevalence of 3.4% observed among patients infected with HBV only. All patients with the triple mutational pattern showed sE164D + sI195M changes in the envelope gene. Multivariate analysis demonstrated that HIV co-infection (adjusted OR 11.2, 95% CI 2.0-61.0) and HBV genotype A (adjusted OR 7.2, 95% CI 1.5-34.8) were the only independent variables associated with the chance of harboring rtM204V. Patients with HBV genotype A or HIV co-infection were more likely to harbor the rtM204V mutation. Patients co-infected with HIV showed multiple mutations more frequently, including the triple mutation that may elicit a vaccine escape phenotype. Among patients co-infected with HIV/HBV, strict HBV DNA monitoring is essential to detect treatment failure and adapt therapy to avoid limitations of future therapeutic options or the emergence of a public health threat.
Assuntos
Antivirais/uso terapêutico , Farmacorresistência Viral , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Lamivudina/uso terapêutico , Mutação de Sentido Incorreto , Adulto , DNA Viral/genética , Feminino , Produtos do Gene env/genética , Produtos do Gene pol/genética , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sequência de DNARESUMO
Drug resistance is a crucial problem emerging frequently during treatment of hepatitis B, resulting in treatment failure and progression of liver damage. A direct sequencing method based on a nested PCR was established to detect mutations in samples with low viral load. Primers were designed to obtain an amplicon encompassing the A, B, C, D and E functional domains of HBV polymerase. Fifty-five samples were tested, containing HBV DNA ranging from 19 to 1700 IU/mL. Sixteen samples were also tested by the commercially available assay INNO-LiPA HBV DR v2. Sequencing was successful for all samples, and mutations were detected in 24/55 (43.6%). When used in parallel with DR v2, concordant results were found in 8/16 samples. In the eight discordant cases, four were resolved by sequencing and not by DR v2, and four had differences in the mutation patterns. Direct sequencing was able to show pol mutations not revealed by DR v2, such as rtV214A, rtQ215H/S, and rtM250V. Genotype and env variations were also established. This highly sensitive sequencing protocol, providing valuable sequencing data from samples with a low viral load, is suitable for detection of mutations at the very early signs of failure of treatment, thereby allowing to maximize the success of early treatment changes.
Assuntos
Produtos do Gene pol/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Glicoproteínas de Membrana/genética , Mutação , Análise de Sequência de DNA/métodos , Antivirais/uso terapêutico , Farmacorresistência Viral/genética , Vírus da Hepatite B/metabolismo , Hepatite B Crônica/tratamento farmacológico , Humanos , Fases de Leitura Aberta , Reação em Cadeia da Polimerase/métodos , Sensibilidade e Especificidade , Falha de Tratamento , Carga ViralRESUMO
Direct population sequencing and reverse hybridization (line probe assay [LiPA])-based methods are the most common methods for detecting hepatitis B virus (HBV) drug resistance mutations, although only mutations present in viral quasispecies with a prevalence of > or =20% can be detected by sequencing, and only known mutations are detected by LiPA. Massively parallel ultradeep pyrosequencing (UDPS; GS FLX platform) was used to analyze HBV quasispecies in reverse transcriptase (RT) and hepatitis B S antigen (HBsAg) from five drug-naive patients and eight drug-resistant patients. Eight primer pairs were used to obtain partially overlapping amplicons, covering the RT gene from codons 1 to 288 and the complete overlapping HBsAg sequence. A 1% mutation frequency was selected as the cutoff based on an error rate estimated on plasmid DNA. This technology enabled simultaneous analysis of between 2,852 and 18,016 clonally amplified fragments from each patient. The results indicate that UDPS has a relative sensitivity much higher than both direct sequencing and LiPA. In addition, the UDPS results are quantitative, allowing establishment of the relative frequency of both known mutations and novel substitutions. Some of the detected RT substitutions led to changes also in HBsAg. On the whole, genotype D presented a higher heterogeneity than genotype A. Considering the high quantity of information that can be provided by a single test from one patient, the short turnaround time, the information on substitution frequency, and the detection of rare variants, there are strong advantages conferred by UDPS, and the new method could play a relevant role in the clinical management of HBV infection and therapy.
Assuntos
Farmacorresistência Viral , Variação Genética , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Hepatite B/virologia , Análise de Sequência de DNA/métodos , Proteínas Virais/genética , Primers do DNA/genética , Genótipo , Humanos , Sensibilidade e EspecificidadeRESUMO
The role of hepatitis B virus (HBV) or hepatitis D virus (HDV) coinfections as determinants of hepatitis C virus (HCV) suppression in the setting of HIV-HCV coinfection are poorly understood. Our aim was to assess whether HCV viral replication may be affected by HBV or HDV coinfection in the setting of immunodeficiency driven by HIV.Among the 138 enrolled patients 28(20.3%) tested HCV RNA negative and 110 (79.7%) tested HCV RNA negative. The HCV RNA negative patients showed an higher rate of HBsAg positivity compared with those tested HCVRNA positive [12/28 (42.9%) and 5/110 (4.6%), respectively]. Patients with HCV-HBV-HDV coinfection had the highest chance of having an undetectable HCV RNA (adjusted odds ratio (AOR): 92.0, 95% confidence interval (CI) 5.7-1483.5, p<0.0001). Furthermore, HBV coinfection per se was also found to be independently associated with negative HCV viraemia (AOR: 18.5, 95% CI 2.4-143.5, p<0.0001). HBsAg-positive patients with negative HCV viraemia maintained undetectable levels over time. Our results support a direct role of HBV and HDV coinfections in suppressing HCV viraemia in HIV infected patients. This effect is durable over time, and is not influenced by HAART including anti-HBV drugs.
Assuntos
Infecções por HIV/complicações , Vírus da Hepatite B , Hepatite C Crônica/complicações , Vírus Delta da Hepatite , Viremia , Adulto , Feminino , Antígenos de Superfície da Hepatite B/sangue , Hepatite C Crônica/sangue , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangueRESUMO
Southern Italy shows the highest rates of liver cancer for Europe, mainly related to infection with hepatitis viruses. We thus described incidence rates of liver cancer and investigated prevalence and determinants of HCV and HBV infections in 4496 individuals randomly selected from the general population of the province of Naples. 7.5% was infected with HCV and 27.6% with HBV (2.2% was HBsAg-positive). Prevalence of both infections increased with age, 23.2% of those aged 65 years or older was HCV-positive and 47.9% were HBV-positive. Intravenous drug use (odds ratio (OR)=16.4 for anti-HCV and 4.7 for anti-HBc), history of blood transfusions (OR=2.8 and 1.5, respectively) and surgery, and household contacts with infected people (OR=2.1 and 1.6, respectively) increased risks for both infections. Sexual intercourse with HCV-positive individuals conveyed a 3-fold higher risk of HCV infection. This study quantified the spread of HCV and HBV in the population of southern Italy heavily affected by liver cancer.
Assuntos
Hepatite B Crônica/epidemiologia , Hepatite C Crônica/epidemiologia , Neoplasias Hepáticas/epidemiologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Distribuição por SexoRESUMO
OBJECTIVE: The aim of the study was to analyze the trends in HIV prevalence among childbearing women through unlinked anonymous testing of newborns. METHODS: Dried-blood specimens, residual to routine metabolic screening of newborns, were collected in Italy during the last quarter of each year, from 1994 to 2002. These samples were tested anonymously for HIV antibodies. RESULTS: Of 844,311 specimens tested, 703 (0.83/1000; 95% confidence interval, 0.76-0.88) resulted as HIV antibody-reactive. Prevalence was 1.05 per 1000 in 1994 and decreased significantly over the following 3 years, reaching 0.60 per 1000 in 1997. Thereafter, a seroprevalence increase was recorded with a figure of 1.01 per 1000 in 1999. A decrease was again observed in 2001 and in 2002, when the seroprevalence rate was significantly lower than that recorded in 1994. During the entire study period, higher prevalence rates were observed in northern Italian regions, where the highest AIDS incidence rates are recorded, and in metropolitan compared with nonmetropolitan areas. The estimated number of children born each year to an HIV-positive mother ranged from 313 to 546. CONCLUSION: The number of children born to an HIV-positive mother calls for continued efforts to prevent vertical transmission of the infection.
Assuntos
Infecções por HIV/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Feminino , Geografia , Anticorpos Anti-HIV/sangue , Soroprevalência de HIV , Humanos , Recém-Nascido , Itália/epidemiologia , Gravidez , Prevalência , População Rural , Estudos Soroepidemiológicos , Fatores de Tempo , População UrbanaRESUMO
Hepatitis C virus (HCV) variability is mainly attributed to the ability of the virus to respond to host immune pressure, acting as a driving force for the evolution of quasispecies. This study was aimed at studying the changes in HVR-1 heterogeneity and the evolution of HCV quasispecies in HIV/HCV-coinfected patients according to the pattern of response to highly active antiretroviral therapy (HAART). Sixteen HIV/HCV-coinfected patients harbouring HCV genotype 1 and who had been on HAART for at least 1 year, 8 showing increasing CD4+ T-cell counts (immunological responders) and 8 showing a stable or decreasing CD4+ T-cell counts (immunological nonresponders), were selected from a prospective cohort study. After 1 year of HAART, 11 patients showed HIV viral load <2.6 log10 cp/ml (virological responders), and 5 showed HIV viral load above this value (virological non-responders). Plasma samples, collected before starting therapy and after 1 year of HAART, underwent clonal sequence analysis for HVR-1 region of HCV. Nonsynonymous/synonymous substitutions ratio (Ka/Ks), aminoacidic complexity (normalized Shannon entropy) and diversity (p-distance), were considered as parameters of quasispecies heterogeneity. After 1 year of HAART, heterogeneity of HVR-1 quasispecies significantly decreased in virological non-responders, whereas the heterogeneity tended to increase in virological responders. The differences in the evolution were less stringent, when considering immunological response. On the other hand, profound qualitative modifications of HVR-1 quasispecies were observed only in patients with both immunological and virological HAART response. On the whole, these findings suggest that, in patients undergoing HAART, the extent of HCV variability and the evolution of HVR-1 quasispecies is influenced by the pattern of response to antiretroviral therapy.
Assuntos
Terapia Antirretroviral de Alta Atividade , Evolução Molecular , Infecções por HIV/complicações , Hepacivirus/classificação , Hepatite C/tratamento farmacológico , Proteínas Virais/genética , Adulto , Contagem de Linfócito CD4 , Feminino , HIV , Infecções por HIV/tratamento farmacológico , Hepacivirus/genética , Hepatite C/complicações , Hepatite C/virologia , Humanos , Masculino , RNA Viral/sangue , Resultado do Tratamento , Carga Viral , Proteínas Virais/classificaçãoAssuntos
Infecções por Citomegalovirus/complicações , Infecções por HIV/complicações , Hepatite C/complicações , Adulto , Anticorpos Antivirais/análise , Linfócitos T CD8-Positivos/imunologia , Citomegalovirus/imunologia , Humanos , Transplante de Fígado/efeitos adversos , Subpopulações de Linfócitos TRESUMO
BACKGROUND: The roles of hepatitis C virus (HCV) viremia and HCV genotype in the immune response to highly active antiretroviral therapy (HAART) are poorly understood. Our aim was to assess the CD4+ cell count recovery after HAART in human immunodeficiency virus (HIV)-infected patients with HCV viremia and HIV-infected patients who tested negative for HCV antibody (HCV-Ab). We also aimed to assess whether the response to HAART in these patients varied according to HCV genotype. METHODS: The analysis focused on 1219 HCV-Ab-negative patients and 284 HCV-viremic patients from a cohort of HIV-infected subjects that includes persons who were antiretroviral naive before initiating HAART after cohort enrollment. HCV RNA load and HCV genotype were determined in plasma specimens obtained and stored during the 6-month period preceding the initiation of HAART. RESULTS: The chance of achieving a CD4+ cell count increase of > or = 100 cells/microL from the pre-HAART level tended to be poorer in HCV-viremic patients than in patients who tested negative for HCV-Ab (adjusted relative hazard [RH], 0.82; 95% confidence interval [CI], 0.66-1.01; P = .06). In contrast, a comparison of patients who had a HCV RNA load >1 x 10(6) IU/mL with patients who had a HCV RNA load of 5-1 x 10(6) IU/mL revealed no significant association between HCV RNA load and achievement of an increased CD4+ cell count (adjusted RH, 0.97; 95% CI, 0.75-1.27; P = .83). There was no clear association between HCV genotype and the probability of achieving a CD4+ cell count increase. CONCLUSIONS: An association between the presence of HCV-Ab and immune reconstitution after HAART has been shown elsewhere. Results of our large, prospective study support a direct role of HCV viremia in the CD4+ cell count response to HAART. Moreover, our results underline the fact that, in individuals coinfected with HIV and HCV, the goal of treating HCV infection is to eradicate HCV, to both slow the rate of HCV progression and limit potential interference with the response to HAART.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Hepacivirus/genética , Hepatite C/sangue , Hepatite C/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Contagem de Linfócito CD4 , Estudos de Coortes , Feminino , Genótipo , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , RNA Viral/sangue , Fatores de Tempo , Carga Viral , ViremiaRESUMO
The prognostic role of GB virus type C (GBV-C) viraemia in HIV-infected subjects treated with highly active antiretroviral therapy (HAART) is still undefined. The aim of this analysis is to assess the relationship between GBV-C infection and response to antiretroviral therapy among HIV-infected subjects initiating HAART when antiretroviral-naive. A prospective, observational study of 400 HIV-infected patients with measurements of GBV-C RNA, hepatitis C virus (HCV) antibodies and HCV RNA determined from plasma stored prior to HAART initiation. Time to virological (achieving HIV RNA < or =500 copies/ml) and immunological success (a CD4+ count increase of > or =200 cells/microl), and the time to virological relapse (confirmed HIV RNA >500 copies/ml) were assessed by Kaplan-Meier methods and Cox proportional hazard regression model. Of the subjects, 117 (29.3%) were GBV-C positive and, overall, 351 (87.8%) patients achieved virological success. After controlling for a number of confounders including HCV RNA, GBV-C viraemic patients experienced a significantly lower risk of HIV rebound than those who were GBV-C negative [relative hazard (RH)=0.56, 95% CI: 0.34-0.93, P=0.03]. Conversely, the probability of achieving initial virological success or CD4+ count response after HAART did not differ between GBV-C-negative and -positive subjects. These results suggest that GBV-C coinfection may play a role in determining the rate of HIV rebound possibly by competing with HIV replication after HIV load has been successfully suppressed by HAART.
Assuntos
Infecções por Flaviviridae/complicações , Vírus GB C , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Adulto , Terapia Antirretroviral de Alta Atividade , Sequência de Bases , Estudos de Coortes , DNA Viral/genética , Feminino , Vírus GB C/genética , Vírus GB C/isolamento & purificação , Anticorpos Anti-Hepatite C/sangue , Humanos , Masculino , Estudos Prospectivos , RNA Viral/sangue , RNA Viral/genética , Viremia/complicações , Viremia/tratamento farmacológicoAssuntos
Infecções por Flaviviridae/complicações , Vírus GB C/fisiologia , Infecções por HIV/complicações , Hepatite Viral Humana/complicações , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/virologia , Adulto , Feminino , Infecções por Flaviviridae/virologia , Hepatite Viral Humana/virologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND/AIMS: HVR-1 quasispecies composition and evolution were investigated in patients chronically infected with genotype 1b HCV, treated with PEG-IFN alpha 2b or STD-IFN alpha 2b plus RBV. METHODS: HVR-1 heterogeneity was assessed by calculating nucleotidic complexity, diversity, synonymous (S) and non-synonymous (NS) substitutions at baseline, after 4 weeks of therapy (T1) and at follow-up (T18). Evolution of viral quasispecies was analysed by constructing phylogenetic trees. RESULTS: No correlation of baseline viremia with heterogeneity was observed. Nucleotidic complexity was lower in patients showing early virological response, and tended to be inversely correlated to viral load decline at 4 weeks of treatment. In the majority of SR, profound changes of quasispecies composition occurred during 4 weeks of treatment, while in NR virtually no major changes of pre-therapy variants were observed. Relapse showed both patterns of quasispecies evolution. Virus quasispecies after follow-up was similar to that found at T1 in both Relapsers and NR patients. CONCLUSIONS: Baseline parameters of HVR-1 heterogeneity seem to be involved in the early response to treatment, and early response is associated with profound variations in the HVR-1 quasispecies. Viral quasispecies surviving early therapeutic pressure are most likely able to give rise to either virus rebound or persistence at T18.
Assuntos
Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Interferon-alfa/uso terapêutico , Ribavirina/uso terapêutico , Proteínas Virais/genética , Adulto , Antivirais/administração & dosagem , Farmacorresistência Viral/genética , Quimioterapia Combinada , Evolução Molecular , Feminino , Variação Genética , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Masculino , Pessoa de Meia-Idade , Filogenia , Polietilenoglicóis , Prognóstico , Proteínas Recombinantes , Ribavirina/administração & dosagemRESUMO
BACKGROUND: Hepatitis virus infections continue to be a major concern in the dialysis setting. We studied levels of hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) RNA contamination in dialysis units to better define the role of the dialysis environment and machines in the nosocomial transmission of hepatitis viruses. METHODS: Possible contamination by hepatitis B virus (HBV) and HCV was studied by collecting environmental samples in 3 dialysis units located in Rome, Italy. Samples and controls were tested for HBsAg by a microparticle enzyme immunoassay, and for HCV RNA, by qualitative transcription-mediated amplification assay. RESULTS: HCV RNA and HBsAg were detected in 1 of 64 (1.6%) and 1 of 64 samples (1.6%), respectively. The only HCV RNA-positive sample was found in 1 dialysis unit on the external surface of the dialysate (inlet-outlet) connector of a dialysis machine used for HCV-negative patients. The only HBsAg-positive sample was found in another dialysis unit on the internal surface of the blood pressure monitor cuff of a dialysis bed dedicated for HBsAg-positive patients. CONCLUSION: A segregation policy for HBsAg-positive patients is a necessary measure despite its high cost-effectiveness; we found HBsAg contamination in the segregated HBV-infected room. Conversely, the finding of HCV RNA contamination on a dialysis machine not dedicated to HCV-positive patients suggests that isolation of HCV-infected dialysis patients and use of dedicated machines are unjustified. Major attention should be given to strict adherence to infection control measures in the dialysis setting.