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1.
Blood Cancer J ; 11(8): 142, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376633

RESUMO

This study evaluated the safety and immunogenicity of BNT162b2 vaccine in patients with hematological malignancies. Antibodies blocking spike binding to immobilized ACE-2 (NAb) correlated with anti-Spike (S) IgG d42 titers (Spearman r = 0.865, p < 0.0001), and an anti-S IgG d42 level ≥3100 UA/mL was predictive of NAb ≥ 30%, the positivity cutoff for NAb (p < 0.0001). Only 47% of the patients achieved an anti-S IgG d42 level ≥3100 UA/mL after the two BNT162b2 inocula, compared to 87% of healthy controls. In multivariable analysis, male patients, use of B-cell targeting treatment within the last 12 months prior to vaccination, and CD19+ B-cell level <120/uL, were associated with a significantly decreased probability of achieving a protective anti-S IgG level after the second BNT162b2 inoculum. Finally, using the IFN-γ ELISPOT assay, we found a significant increase in T-cell response against the S protein, with 53% of patients having an anti-S IgG-positive ELISPOT after the second BNT162b2 inoculum. There was a correlation between the anti-S ELISPOT response and IgG d42 level (Spearman r = 0.3026, p = 0.012). These findings suggest that vaccination with two BNT162b2 inocula translates into a significant increase in humoral and cellular response in patients with hematological malignancies, but only around half of the patients can likely achieve effective immune protection against COVID-19.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/complicações , COVID-19/imunologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/imunologia , Imunogenicidade da Vacina , SARS-CoV-2/imunologia , Imunidade Adaptativa , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Vacinas contra COVID-19/administração & dosagem , Comorbidade , Feminino , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Linfócitos T/imunologia , Linfócitos T/metabolismo , Adulto Jovem
2.
JMIR Res Protoc ; 10(4): e24731, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33821807

RESUMO

BACKGROUND: Previous large-scale studies have examined the effect of chronic hepatitis B virus (HBV) infection on overall and cause-specific mortality in individuals with HIV. However, few studies have collected data on the subclinical indicators of HBV that lead to these severe outcomes in the coinfected population. OBJECTIVE: In this study, we aim to describe the procedures of a cohort study extension aimed at assessing HBV-DNA replication, serological markers of HBV (hepatitis B e antigen [HBeAg] and hepatitis B surface antigen), and liver fibrosis and how these subclinical outcomes relate to mortality in predominately tenofovir-treated, coinfected patients with HIV-HBV. We assessed the characteristics at cohort inclusion of those who participated in the cohort extension, as well as those who did not participate due to being lost to follow-up or death. METHODS: Patients with HIV and chronic HBV who completed follow-up in a prospective cohort study conducted in 4 outpatient centers (Paris and Lyon, France; 2002-2011) were invited to participate in a cross-sectional visit from November 2016 to March 2018, during which a comprehensive evaluation of HIV- and HBV-related disease was undertaken. Virological and clinical data since the previous study visit were retrospectively collected. RESULTS: Of the 308 individuals enrolled in the cohort, 147 (47.7%) participated in the cross-sectional study. At this visit, most participants were HBeAg negative (111/134, 82.8% with available data), had undetectable HBV DNA (124/132, 93.9% with available data), and were undergoing antiretroviral therapy containing tenofovir disoproxil fumarate or tenofovir alafenamide (114/147, 77.6%). There were no significant differences in characteristics at cohort inclusion between those who did and did not complete the cross-sectional visit, except for a lower proportion with an AIDS-defining illness (30/147, 20.5% vs 49/161, 30.4%, respectively; P=.04). Of the 161 nonparticipating individuals, 42 (26.1%) died, 41 (25.4%) were lost to follow-up and known to be alive, and 78 (48.4%) were lost to follow-up with unknown vital status. Most differences in characteristics at cohort inclusion were observed between deceased individuals and those participating in the cross-sectional visit or those lost to follow-up. With this extension, the median follow-up time of the overall cohort is presently 9.2 years (IQR 3.4-14.6). CONCLUSIONS: Extended follow-up of the French HIV-HBV cohort will provide important long-term data on the subclinical trajectory of HBV disease in the coinfected population. The biases due to the relatively high rate of those lost to follow-up need to be assessed in future studies of this cohort. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/24731.

3.
Eur J Clin Microbiol Infect Dis ; 40(10): 2235-2241, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33782783

RESUMO

We report evaluation of 30 assays' (17 rapid tests (RDTs) and 13 automated/manual ELISA/CLIA assay (IAs)) clinical performances with 2594 sera collected from symptomatic patients with positive SARS-CoV-2 rRT-PCR on a respiratory sample, and 1996 pre-epidemic serum samples expected to be negative. Only 4 RDT and 3 IAs fitted both specificity (> 98%) and sensitivity (> 90%) criteria according to French recommendations. Serology may offer valuable information during COVID-19 pandemic, but inconsistent performances observed among the 30 commercial assays evaluated, which underlines the importance of independent evaluation before clinical implementation.


Assuntos
Anticorpos Antivirais/sangue , Teste Sorológico para COVID-19/métodos , COVID-19/sangue , Imunoensaio/métodos , SARS-CoV-2/imunologia , COVID-19/virologia , Humanos , Imunoensaio/economia , Imunoglobulina M/sangue , Kit de Reagentes para Diagnóstico , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Sensibilidade e Especificidade
4.
Diagn Microbiol Infect Dis ; 100(3): 115366, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33756311

RESUMO

RT-PCR is the reference method for diagnosis of a Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infection. During the setting up of 6 SARS-CoV-2 RT-PCR assays in our laboratory, comparative evaluations were systematically undertaken and allowed to evidence major discrepancies on cycle threshold RT-PCR results between techniques. These tendencies were confirmed in routine application when analyzing sequential samples from the same patients. Our aim was to examine the impact of the technique among factors influencing RT-PCR result, a far surrogate of 'viral load' in the heterogeneous environment of respiratory specimens.


Assuntos
Teste de Ácido Nucleico para COVID-19/estatística & dados numéricos , COVID-19/virologia , SARS-CoV-2/isolamento & purificação , COVID-19/diagnóstico , Teste de Ácido Nucleico para COVID-19/métodos , Conjuntos de Dados como Assunto , Testes Diagnósticos de Rotina , Genoma Viral , Humanos , Nasofaringe/virologia , RNA Viral/genética , SARS-CoV-2/genética , Carga Viral
6.
Bone Marrow Transplant ; 55(3): 586-594, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31562397

RESUMO

This retrospective study evaluated the impact of a pre-emptive rituximab (RTX) strategy for Epstein-Barr virus (EBV) reactivation on immune recovery and outcomes of 219 high-risk recipients undergoing allogeneic stem cell transplantation (allo-SCT) for hematological malignancies or bone marrow failure. One-hundred and seven patients received pre-emptive RTX for EBV reactivation (RTX group) and 112 did not (control group). The median onset time of EBV reactivation was 49 days (range, 14-561), including five patients who developed post-transplant lymphoproliferative disorder (EBV-PTLD). RTX and control groups were pair-matched to assess the impact of RTX on all endpoints. In RTX patients, CD19 + B cells were significantly decreased until 1-year post-transplant, so were immunoglobulin levels. Twenty-one patients (17%) developed RTX-related neutropenia. There was, in the RTX group, a trend towards a lower cumulative incidence of chronic GvHD (P = 0.059). Overall survival, progression-free survival, non-relapse mortality, relapse incidence, and incidence of overall infections at 2 years following allo-SCT were comparable in the two groups. We conclude that pre-emptive RTX, despite inducing a delayed B-cell reconstitution and a high risk of RTX-related neutropenia, may be considered as a worthwhile treatment, given the absence of negative impact on post allo-SCT outcomes and a low incidence of EBV-PTLD.


Assuntos
Infecções por Vírus Epstein-Barr , Transplante de Células-Tronco Hematopoéticas , Transtornos Linfoproliferativos , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpesvirus Humano 4 , Humanos , Recidiva Local de Neoplasia , Estudos Retrospectivos , Rituximab/uso terapêutico
7.
Protein Expr Purif ; 162: 44-50, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31145974

RESUMO

BALF0/1 is a putative Epstein-Barr virus (EBV) protein that has been described as a modulator of apoptosis. So far, the lack of specific immunological reagents impaired the detection of native BALF0/1 in EBV-infected cells. This study describes the expression and purification of a truncated form of BALF0/1 (tBALF0) using a heterologous bacterial expression system. tBALF0 was further used as an antigen in an indirect Enzyme-linked Immunosorbent Assay (ELISA) that unraveled the presence of low titer IgGs to BALF0/1 during primary (10.0%) and past (13.3%) EBV infection. Conversely high-titer IgGs to BALF0/1 were detected in 33.3% of nasopharyngeal carcinoma (NPC) patients suggesting that BALF0/1 and/or humoral response against it may contribute to NPC pathogenesis.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Vírus Epstein-Barr/sangue , Herpesvirus Humano 4/imunologia , Imunoglobulina G/sangue , Carcinoma Nasofaríngeo/sangue , Proteínas Virais/imunologia , Anticorpos Antivirais/imunologia , Ensaio de Imunoadsorção Enzimática , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/genética , Humanos , Imunidade Humoral , Imunoglobulina G/imunologia , Carcinoma Nasofaríngeo/virologia , Proteínas Virais/genética
8.
Open Forum Infect Dis ; 5(10): ofy227, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30324127

RESUMO

Background: Occult hepatitis B infection (OBI) is recognized as a risk factor for cirrhosis and hepato-cellular carcinoma. However, OBI brings together a large spectrum of patients who might harbor different characteristics and prognosis. Methods: We analyzed the databases of a university hospital in Paris to identify OBI among patients (n = 3966) concomitantly tested for hepatitis B virus (HBV) DNA and serology during a 7-year period. OBI patients were gathered into clinical entities according to their clinical records. Results: Forty-seven OBIs were identified (1.2%). All patients had detectable anti-HBc, isolated (n = 26) or associated with anti-HBs (n = 21). The proportion of OBIs was 3.4% for patients with isolated anti-HBc and 4.2% for patients with both anti-HBc and anti-HBs. Four clinical categories of OBI patients were identified: patients with a passed HBV infection with HBs Ag clearance (group A, 23.4%); HBV-exposed patients receiving immunosuppressive therapy (group B, 29.8%); HIV/HBV-coinfected patients with therapy discontinuation (group C, 17%); HBV-exposed patients with severe liver conditions (group D, 29.8%). Significant follow-up was available for 32 patients, showing a more deleterious prognosis in group D patients, associated more with their underlying condition than the OBI status. Conclusions: OBI is a heterogeneous condition with various clinical implications.

9.
World J Gastroenterol ; 23(38): 7037-7046, 2017 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-29097876

RESUMO

AIM: To determine whether hepatitis B virus (HBV)-testing could serve as a gateway to vaccinate non-immunized individuals in a low-prevalent country. METHODS: Non-immunized subjects participating in a multi-center, HBV-testing campaign in Paris, France were identified and contacted via telephone 3-9 mo after testing in order to determine vaccination status. Vaccination coverage was evaluated in per-protocol (for all respondents) and intent-to-treat analysis (assuming all non-responders did not vaccinate). RESULTS: In total, 1215/4924 (24.7%) enrolled subjects with complete HBV serology were identified as non-immunized and eligible for analysis. There were 99/902 successfully contacted subjects who had initiated HBV vaccination after screening: per-protocol, 11.0% (95%CI: 9.0-13.2); intent-to-treat, 8.2% (95%CI: 6.7-9.8). In multivariable analysis, vaccination was more likely to be initiated in individuals originating from moderate or high HBV-endemic countries (P < 0.001), patients with limited healthcare coverage (P = 0.01) and men who have sex with men (P = 0.02). When asked about the reasons for not initiating HBV vaccination, the most frequent response was "will be vaccinated later" (33.4%), followed by "did not want to vaccinate" (29.8%), and "vaccination was not proposed by the physician" (21.5%). Sub-group analysis indicated a stark contrast in vaccination coverage across centers, ranging from 0%-56%. CONCLUSION: HBV-vaccination after HBV screening was very low in this study, which appeared largely attributed to physician-patient motivation towards vaccination. Increased vaccination coverage might be achieved by emphasizing its need at the organizational level.


Assuntos
Vacinas contra Hepatite B , Vírus da Hepatite B/isolamento & purificação , Hepatite B/diagnóstico , Programas de Rastreamento , Vacinação/estatística & dados numéricos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
J Clin Virol ; 95: 55-60, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28869890

RESUMO

BACKGROUND: Hepatitis B surface antigen (HBsAg)-seroconversion, or loss of HBsAg and acquisition of anti-hepatitis B surface (HBs) antibodies, defines functional cure of chronic hepatitis B virus (HBV) infection. After HBsAg-loss, little is known regarding the development of anti-HBs antibodies and even less so in individuals co-infected with HIV. OBJECTIVES: To determine anti-HBs antibody kinetics after HBsAg-loss and explore determinants of HBsAg-seroconversion in HIV-HBV co-infected patients. STUDY DESIGN: Patients enrolled in the French HIV-HBV cohort were included if they had >1 study visit after HBsAg-loss. Individual patient kinetics of anti-HBs antibody levels were modeled over time using mixed-effect non-linear regression, whereby maximum specific growth rate and maximal level of antibody production were estimated from a Gompertz growth equation. RESULTS: Fourteen (4.6%) of 308 co-infected patients followed in the cohort exhibited HBsAg-loss, all of whom were undergoing antiretroviral therapy. Nine (64.3%) of these patients achieved HBsAg-seroconversion during a median 3.0 years (IQR=1.1-5.1) after HBsAg-loss. Across individuals with HBsAg-seroconversion, the fastest rates of antibody growth ranged between 0.57-1.93year-1 (population maximum growth rate=1.02) and antibody production plateaued between 2.09-3.66 log10 mIU/mL at the end of follow-up (population maximal antibody levels=2.66). Patients with HBsAg-seroconversion had substantial decreases in HBV DNA viral loads (P=0.03) and proportion with elevated ALT levels (P=0.02) and HBeAg-positive serology (P=0.08). No such differences were observed in those without HBsAg-seroconversion. CONCLUSIONS: Most co-infected patients with HBsAg-seroconversion produced and maintained stable antibody levels, yet kinetics of anti-HBs production were much slower compared to those observed post-vaccination or after clearance of acute HBV-infection.


Assuntos
Coinfecção , Infecções por HIV/complicações , Anticorpos Anti-Hepatite B/biossíntese , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Antígenos E da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Adulto , DNA Viral/sangue , Feminino , Infecções por HIV/virologia , Anticorpos Anti-Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Soroconversão , Testes Sorológicos , Carga Viral
11.
Eur J Gastroenterol Hepatol ; 28(6): 633-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26954517

RESUMO

OBJECTIVES: Worldwide, many infected individuals are unaware of their hepatitis B virus (HBV) status. We evaluated the effectiveness of HBV rapid testing in promoting linkage-to-care. METHODS: In 2012, volunteers were recruited from five Parisian centers. Participants were randomized 1 : 1 to receive standard serology (S) or rapid testing (VIKIA-HBsAg/Quick Profile anti-HBsAb) with confirmatory serology (R+S). The primary endpoint was percentage of individuals with appropriate linkage-to-care (nonimmunized individuals starting vaccination or HBsAg-positive individuals receiving medical evaluation). The secondary outcomes were percentage receiving HBV-test results and performance of HBV rapid tests. RESULTS: In total, 995 individuals were screened. Among the HBV-infection groups included in the primary endpoint (n=409), 20 (4.9%) received appropriate linkage-to-care, with no difference between S and R+S groups (5.7 vs. 4.1%, P=0.5). Two of eight HBsAg-positive participants had a medical visit (1/6 and 1/2 in the S and R+S groups, respectively) and 18/401 (4.5%) nonimmunized participants initiated HBV-vaccination (11/205 and 7/196). Factors that tended to be associated with linkage-to-care were female sex, birth country of high HBV prevalence, and extended medical stay. Test results were not obtained in 4.7% of participants, which was significantly higher in the S arm (P=0.02). Both sensitivity and specificity were 100% for the VIKIA-HBsAg rapid test and 94.4 and 80.8%, respectively, for the anti-HBsAb Quick Profile rapid test. CONCLUSION: Despite a higher proportion of participants obtaining their results in the R+S arm and better performance of anti-HBsAb rapid tests than described previously, we found no evidence that HBV screening based initially on rapid tests leads to increased HBV-vaccination rates or medical evaluation. This strategy should be evaluated in more hard-to-reach populations.


Assuntos
Hepatite B/diagnóstico , Encaminhamento e Consulta , Adulto , Feminino , Hepatite B/imunologia , Hepatite B/prevenção & controle , Hepatite B/terapia , Anticorpos Anti-Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/uso terapêutico , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Paris , Fatores Sexuais , Fatores de Tempo , Adulto Jovem
12.
J Gastroenterol Hepatol ; 31(10): 1750-1756, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26992056

RESUMO

BACKGROUND AND AIM: The impact of basal core promoter (BCP) and precore (PC) mutants of the hepatitis B virus (HBV) on liver disease severity remains controversial. The aim of the present study was to screen BCP and PC mutations in 252 HBV surface antigen (HBsAg) positive carriers in France and to assess relationships between these mutations and severe fibrosis. METHODS: Direct sequencing of the precore/core gene was used to detect A1762T/G1764A and G1757A mutations in the BCP and G1896A and G1899A mutations in the PC region. RESULTS: The prevalences of A1762T/G1764A, G1757A, G1896A, and G1899A mutations were 34.1%, 38.7%, 54.9%, and 29.3% (P < 0.001), respectively. The independent predictors of severe fibrosis (≥F3 Metavir) were older age (P < 0.001), male gender (P = 0.012), elevated alanine aminotransferase (P < 0.001), and the double A1762T/G1764A mutant with no other mutations (P = 0.011). Interestingly, the association of the G1899A mutation with the double A1762T/G1764A mutant significantly counteracted the deleterious effect of the sole double A1762T/G1764A mutant (odds ratio [OR] = 0.28 vs. OR = 3.55, respectively, P = 0.028). CONCLUSIONS: Patients with the A1762T/G1764A mutation have a higher risk of severe fibrosis. The G1899A mutation is a protective factor against severe fibrosis that counteracted the deleterious effect of the A1762T/G1764A mutation. Finally, host phenotypic and HBV genotypic markers independently predict fibrosis severity.


Assuntos
Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Cirrose Hepática/virologia , Mutação , Adulto , Fatores Etários , Idoso , DNA Viral/análise , DNA Viral/genética , Feminino , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Virulência/genética
13.
Open Forum Infect Dis ; 2(4): ofv162, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26668814

RESUMO

Background. In Europe and the United States, more than two thirds of individuals infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) and 15%-30% of human immunodeficiency virus (HIV)-positive individuals are unaware of their infection status. Simultaneous HIV-, HBV-, and HCV-rapid tests could help improve infection awareness and linkage-to-care in particularly vulnerable populations. Methods. The OptiScreen III study was a single-center, randomized, control trial conducted at a free clinic ("Médecins du Monde", Paris, France). Participants were randomized 1:1 to receive 1 of 2 interventions testing for HIV, HBV, and HCV: standard serology-based testing (S-arm) or point-of-care rapid testing (RT-arm). The main study endpoints were the proportion of participants who became aware of their HIV, HBV, and HCV status and who were linked to care when testing positive. Results. A total of 324 individuals, representing mainly African immigrants, were included. In the S-arm, 115 of 162 (71.0%) participants performed a blood draw and 104 of 162 (64.2%) retrieved their test result. In comparison, 159 of 162 (98.2%) of participants randomized to the RT-arm obtained their results (P < .001). Of the 38 (11.7%) participants testing positive (HIV, n = 7; HBV, n = 23; HCV, n = 8), 15 of 18 (83.3%) in the S-arm and 18 of 20 (90.0%) in the RT-arm were linked-to-care (P = .7). In post hoc analysis assuming the same disease prevalence in those without obtaining test results, difference in linkage-to-care was more pronounced (S-arm = 60.0% vs RT-arm = 90.0%; P = .04). Conclusions. In a highly at-risk population for chronic viral infections, the simultaneous use of HIV, HBV, and HCV point-of-care tests clearly improves the "cascade of screening" and quite possibly linkage-to-care.

14.
AIDS ; 29(15): 1963-73, 2015 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-26153669

RESUMO

OBJECTIVE: This study determines rates and risk factors associated with hepatitis B surface antigen (HBsAg) and hepatitis B 'e' antigen (HBeAg) seroclearance, two important prognostic indicators during infection with hepatitis B virus (HBV), in a large contemporary cohort of patients coinfected with HIV-HBV. DESIGN: Prospective cohort study of predominately antiretroviral therapy (ART) experienced, coinfected patients. METHODS: Participants enrolled in the French HIV-HBV Cohort had complete HBV serological battery conducted at inclusion and every yearly visit. Piecewise-exponential survival models were used to determine risk factors associated with seroclearance. RESULTS: A total of 290 patients, of whom 151 (52.1%) were HBeAg positive, had been followed for a median 7.4 years (interquartile range [IQR] = 3.1-8.0). Tenofovir (TDF) containing ART became increasingly more frequent, as rates of undetectable HBV-DNA increased accordingly (at baseline = 39.3%, end of follow-up = 91.0%). In HBeAg-positive patients, 60 of 151 had HBeAg seroclearance (cumulative 46.4% at end of follow-up) after a median 3.0 years (IQR = 2.0-4.9). Overall, 17 of 290 patients had HBsAg seroclearance (cumulative 7.4% at end of follow-up) after a median 4.6 years (IQR = 2.1-7.2). Lower levels of time-averaged cumulative HBV-DNA were significantly associated with both HBeAg and HBsAg seroclearance (P < 0.001 and P = 0.01, respectively). In post hoc analysis among patients initiating TDF, incidence rates of HBeAg seroclearance peaked at year 4 of TDF treatment (13.1/100 person-years), whereas a steep drop in HBsAg seroclearance incidence rates occurred after year 3 (at year 3 = 1.2/100 person-years versus thereafter = 0.6/100 person-years). CONCLUSION: HBsAg seroclearance and, to a lesser extent, HBeAg seroclearance remain difficult endpoints for patients coinfected with HIV-HBV to achieve. HBV-DNA suppression, associated with effective treatment, is strongly linked to seroclearance, but this mostly occurs within the first years of ART-containing highly potent anti-HBV activity.


Assuntos
Antirretrovirais/uso terapêutico , Coinfecção/virologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/complicações , Adulto , DNA Viral/sangue , Feminino , França , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
15.
J Int AIDS Soc ; 18: 19888, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26004637

RESUMO

OBJECTIVES: Data on the extent of drug use and associated HIV, hepatitis C and hepatitis B infection in West Africa are lacking. The objectives of ANRS12244 UDSEN study were to estimate the size of the heroin and/or cocaine drug user (DU) population living in the Dakar area (Senegal), and assess the prevalence and risk factors of HIV, hepatitis C virus (HCV) and hepatitis B virus (HBV), including behavioural determinants in this population, in order to set up an integrated prevention and treatment programme for DUs. DESIGN AND METHODS: A capture-recapture method was applied for population size estimation, whereas the respondent-driven sampling (RDS) method was used to recruit a sample of DUs living in the Dakar area and determine HIV, HBV and HCV prevalence. Behavioural data were gathered during face-to-face interviews, and blood samples were collected on dried blood spots for analysis in a central laboratory. Data analysis was performed using the RDS analysis tool, and risk factors were determined by logistic regression. Access to laboratory results was organized for the participants. RESULTS: The size of the DU population in the Dakar area was estimated to reach 1324 (95% confidence interval (95% CI: 1281-1367)). Based on the 506 DUs included in the study, the HIV, HCV and HBV prevalence were 5.2% (95% CI: 3.8-6.3), 23.3% (95% CI: 21.2-25.2) and 7.9% (95% CI: 5.2-11.1), respectively. In people who inject drugs (PWID), prevalence levels increased to 9.4% for HIV and 38.9% for HCV (p=0.001 when compared to those who never injected). Women were more at risk of being HIV infected (prevalence: 13.04% versus 2.97% in males, p=0.001). Being PWID was a risk factor for HCV and HIV infection (odds ratio, OR: 2.7, 95% CI: 1.7-4.3, and OR: 4.3, 95% CI: 1.7-10.7, respectively), whereas older age and female sex were additional risk factors for HIV infection (10% increase per year of age, p=0.03 and OR: 4.9, 95% CI: 1.6-156, respectively). No specific determinant was associated with the risk of HBV infection. CONCLUSIONS: High HIV and HCV prevalence were estimated in this population of DUs (including non-injectors) living in the Dakar area, Senegal, whereas HBV prevalence was close to that of the global Senegalese population, reflecting a risk of infection independent of drug use. Women seem to be highly vulnerable and deserve targeted interventions for decreasing exposure to HIV, while behavioural risk factors for HIV and HCV include the use of unsafe injections, reflecting the urgent need for developing harm reduction interventions and access to opioid substitution therapy services.


Assuntos
Usuários de Drogas , Infecções por HIV/epidemiologia , Hepatite C/epidemiologia , Adulto , Feminino , Infecções por HIV/etiologia , Redução do Dano , Hepatite B/epidemiologia , Hepatite B/etiologia , Hepatite C/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Assunção de Riscos , Transtornos Relacionados ao Uso de Substâncias/complicações
16.
J Clin Microbiol ; 53(7): 2195-202, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25926499

RESUMO

The pretherapeutic presence of protease inhibitor (PI) resistance-associated variants (RAVs) has not been shown to be predictive of triple-therapy outcomes in treatment-naive patients. However, they may influence the outcome in patients with less effective pegylated interferon (pegIFN)-ribavirin (RBV) backbones. Using hepatitis C virus (HCV) population sequence analysis, we retrospectively investigated the prevalence of baseline nonstructural 3 (NS3) RAVs in a multicenter cohort of poor IFN-RBV responders (i.e., prior null responders or patients with a viral load decrease of <1 log IU/ml during the pegIFN-RBV lead-in phase). The impact of the presence of these RAVs on the outcome of triple therapy was studied. Among 282 patients, the prevalances (95% confidence intervals) of baseline RAVs ranged from 5.7% (3.3% to 9.0%) to 22.0% (17.3% to 27.3%), depending to the algorithm used. Among mutations conferring a >3-fold shift in 50% inhibitory concentration (IC50) for telaprevir or boceprevir, T54S was the most frequently detected mutation (3.9%), followed by A156T, R155K (0.7%), V36M, and V55A (0.35%). Mutations were more frequently found in patients infected with genotype 1a (7.5 to 23.6%) than 1b (3.3 to 19.8%) (P = 0.03). No other sociodemographic or viroclinical characteristic was significantly associated with a higher prevalence of RAVs. No obvious effect of baseline RAVs on viral load was observed. In this cohort of poor responders to IFN-RBV, no link was found with a sustained virological response to triple therapy, regardless of the algorithm used for the detection of mutations. Based on a cross-study comparison, baseline RAVs are not more frequent in poor IFN-RBV responders than in treatment-naive patients and, even in these difficult-to-treat patients, this study demonstrates no impact on treatment outcome, arguing against resistance analysis prior to treatment.


Assuntos
Antivirais/farmacologia , Farmacorresistência Viral , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/virologia , Inibidores de Proteases/farmacologia , Adulto , Idoso , Antivirais/uso terapêutico , Feminino , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/tratamento farmacológico , Humanos , Concentração Inibidora 50 , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Oligopeptídeos/farmacologia , Oligopeptídeos/uso terapêutico , Prolina/análogos & derivados , Prolina/farmacologia , Prolina/uso terapêutico , Inibidores de Proteases/uso terapêutico , Estudos Retrospectivos , Ribavirina/uso terapêutico , Resultado do Tratamento , Proteínas não Estruturais Virais/genética
17.
Liver Int ; 35(3): 795-804, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24606220

RESUMO

BACKGROUND & AIMS: In patients infected with hepatitis B virus (HBV) and HIV, hepatitis B 'e' antigen (qHBeAg) and hepatitis B surface antigen quantification (qHBsAg) may be used to predict short-term HBeAg and HBsAg loss, respectively. To determine if these quantifiable markers also provide accurate prediction of antigen loss during long-term, extensive tenofovir (TDF) treatment and to further establish qHBsAg profiles associated with HBsAg seroconversion. METHODS: Prospective study of 111 co-infected, antiretroviral-experienced patients undergoing a TDF-containing regimen for >12 months. HBV-DNA viral load, qHBeAg [Paul Ehrlich Institute Units (PEIU)/ml] and qHBsAg were quantified at baseline and every 6-12 months. Sensitivity (Se) and specificity (Sp) of qHBeAg criteria were calculated using a time-dependent receiver operator characteristic curve, and qHBsAg profiles were developed using a group-based trajectory model. RESULTS: After a median 74.2 months (IQR: 33.1-94.7) of TDF treatment, four patients had HBsAg seroconversion. Among the 78 (70.3%) HBeAg-positive patients, cumulative proportion with HBeAg loss was 42.0% (n = 23) at month 96. Baseline qHBeAg ≤100 PEIU/ml was the only significant factor for HBeAg loss (adjusted-HR = 2.36, 95% CI: 1.02-5.46) in multivariable analysis. In terms of predicting HBeAg-loss until month 96, qHBeAg ≤10 PEIU/ml was more accurate when evaluated at month 24 (Se = 0.73, Sp = 0.80) than month 12 (Se = 0.48, Sp = 0.90). All four patients with HBsAg seroconversion had profiles with large decreases in qHBsAg (>2 log10 IU/ml), not necessarily occurring during the first 12 months, which was infrequent in patients without seroconversion (8.4%, P < 0.001). CONCLUSIONS: Quantifying hepatitis 'e' antigen during the first 2 years of TDF treatment is a practical tool in predicting long-term HBeAg loss. Non time-specific declines in qHBsAg may be a useful indicator of HBsAg seroconversion.


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Organofosfonatos/uso terapêutico , Adenina/uso terapêutico , Adulto , Coinfecção/tratamento farmacológico , DNA Viral/isolamento & purificação , Feminino , Vírus da Hepatite B/genética , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Sensibilidade e Especificidade , Tenofovir , Carga Viral
18.
Hepatology ; 60(2): 497-507, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24752996

RESUMO

UNLABELLED: Tenofovir (TDF) is considered the ideal treatment for patients coinfected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV). However, certain coinfected patients exhibit incomplete viral suppression, with persistent, and sometimes transient, bouts of HBV replication. The reasons for this, including clinical effect, are unclear. A total of 111 HIV-HBV-infected patients undergoing TDF-containing antiretroviral therapy were prospectively followed. Serum HBV-DNA viral load, hepatitis surface (HBsAg) and e antigen (HBeAg) status were obtained at baseline and every 6-12 months. Amino acid (aa) changes on the polymerase gene were assessed using direct sequencing after nested polymerase chain reaction in patients with persistent viremia (PV). After a median of 74.7 months (interquartile range: 33.4-94.7), virological response (VR; <60 IU/mL) occurred in 96 of 111 (86.5%) patients. Of these, 86 of 96 (89.6%) remained completely undetectable during follow-up (stabilized VR). The remaining 10 of 96 (10.4%) patients had a transient blip of detectable HBV-DNA (transient PV), during which time 9 of 9 (100%) with available samples had detectable plasma TDF. Low-level PV (LL-PV; 61-2,000 IU/mL) was observed in 11 of 111 (9.9%) patients, the majority of which had detectable plasma TDF (8 of 9; 88.9%). High-level PV (>2,000 IU/mL) was rare (4 of 111; 3.6%) and was associated with nonadherence. At TDF initiation, patients with stabilized VR had significantly higher nadir CD4(+) count, compared to those with transient PV (P = 0.006) or LL-PV (P = 0.04). No consistent aa changes, other than those associated with lamivudine resistance, were observed in patients with persistent viremia. Importantly, HBeAg loss, HBeAg seroconversion, and HBsAg loss only occurred in patients with stabilized VR. Two patients with stabilized VR developed hepatocellular carcinoma and 2 with LL PV died, 1 of a liver-related cause. CONCLUSION: Suboptimal HBV control during TDF treatment has a negative effect on serological outcomes, but not necessarily clinical events. Immunoregulation may provide more insight into this phenomenon.


Assuntos
Adenina/análogos & derivados , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Organofosfonatos/administração & dosagem , Viremia/tratamento farmacológico , Adenina/administração & dosagem , Adulto , Coinfecção/sangue , DNA Viral/sangue , DNA Viral/genética , Farmacorresistência Viral , Feminino , Seguimentos , Genótipo , Infecções por HIV/sangue , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores da Transcriptase Reversa/administração & dosagem , Tenofovir , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Viremia/sangue , Replicação Viral/efeitos dos fármacos
19.
PLoS One ; 9(3): e92266, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24663387

RESUMO

BACKGROUND: In low hepatitis B virus (HBV)-prevalent countries, most HBV-infected persons are unaware of their status. We aimed to evaluate whether (i) previous HBV-testing, (ii) physicians decision to screen, and (iii) CDC's recommendations identified infected individuals and which risk-factor groups needing testing. METHODS: During a mass, multi-center HBV-screening study from September 2010-August 2011, 3929 participants were screened for hepatitis B surface antigen (HBsAg), anti-HBs and anti-Hepatitis B core antibodies (anti-HBcAb). Questions on HBV risk-factors and testing practices were asked to participants, while participants' eligibility for HBV-testing was asked to study medical professionals. RESULTS: 85 (2.2%) participants were HBsAg-positive, while 659 (16.8%) had either resolved HBV infection or isolated anti-HBcAb. When comparing practices, HBV-testing was more likely to occur in HBV-infected participants if Centers for Disease Control and Prevention (CDC) recommendations were used (Sensitivity = 100%, 95%CI: 95.8-100) than physicians' discretion (Sensitivity = 87.1%, 95%CI: 78.0-93.4) or previous HBV-test (Sensitivity = 36.5%, 95%CI: 26.3-47.6) (p<0.0001). Nevertheless, many non-infected individuals would still have been screened using CDC-recommendations (Specificity = 31.1%, 95%CI: 29.6-32.6). Using multivariable logistic regression, HBsAg-positive status was significantly associated with the following: males, originating from high HBV-endemic region, contact with HBV-infected individual, without national healthcare, and intravenous-drug user (IDU). Of these risk-factors, physician's discretion for testing HBV was not significantly associated with participants' geographical origin or IDU. CONCLUSIONS: Missed opportunities of HBV-screening are largely due to underestimating country of origin as a risk-factor. Applying CDC-recommendations could improve HBV-screening, but with the disadvantage of many tests. Further development of HBV-testing strategies is necessary, especially before severe disease occurs.


Assuntos
Cidades/epidemiologia , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Hepatite B/diagnóstico , Programas de Rastreamento/estatística & dados numéricos , Adulto , Centers for Disease Control and Prevention, U.S. , Feminino , Hepatite B/sangue , Hepatite B/epidemiologia , Antígenos de Superfície da Hepatite B/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Médicos , Prevalência , Fatores de Risco , Inquéritos e Questionários , Estados Unidos
20.
AIDS ; 27(8): 1356-9, 2013 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-23925383

RESUMO

The efficacy and tolerance of telaprevir (TVR) was examined in 20 mostly cirrhotic HIV-hepatitis C genotype 1 (HCV-G1)-infected patients failing previous treatment with pegylated-interferon and ribavirin (PR). HCV-RNA less than 12 IU/ml was observed in 35.3% of patients at W2, 55.0% at W4, 65.0% at W12 and 55.0% at W24. All patients with virological failure (n = 9) exhibited V36M/R155K mutations. Early virological response was a determinant of HCV-RNA less than 12 IU/ml at W24 (P < 0.001). No grade 3-4 dermatological side-effects were reported. TVR-PR tritherapy appeared to be rather effective and well tolerated among difficult-to-treat HIV-HCV-G1 patients.


Assuntos
Antivirais/administração & dosagem , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Oligopeptídeos/administração & dosagem , Polietilenoglicóis/administração & dosagem , Antivirais/uso terapêutico , Coinfecção , Infecções por HIV/complicações , Hepacivirus/genética , Hepatite C Crônica/complicações , Humanos , Interferon-alfa/efeitos adversos , Oligopeptídeos/efeitos adversos , Polietilenoglicóis/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
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