Quantitative HBsAg an unreliable marker for diagnosis and disease progression in genotype F chronic HBeAg-negative infections

Quantitative hepatitis B surface antigen (qHBsAg) has been proposed as a biomarker to distinguish HBeAg-negative chronic infections (ENI) from HBeAg-negative chronic hepatitis (ENH), identify patients prone to achieving sustained HBsAg loss, and predict the risk of liver disease progression. There is evidence that qHBsAg varies among genotypes, however there is a paucity of data on genotype F. The aim of this study was to investigate the performance of qHBsAg in the diagnosis and evolution of genotype F chronic HBeAg-negative infections. HBV-DNA and HBsAg levels from 153 patients with ENI were correlated with the genotype. Liver disease progression was assessed by abdominal ultrasound and a transient elastography. The qHBsAg levels were significantly different among genotypes (p 3.0 log10 IU/ml, no cases of advanced liver disease were observed at the end of follow-up. This study provides new insights into the impact of HBV genotypes, in particular GTF, on serum HBsAg levels, emphasizing the need to implement a genotype-specific cut-off to achieve diagnostic certainty in the identification of ENI and the risk of liver disease progression. Regardless of HBV genotype, qHBsAg has been shown to be a powerful and reliable biomarker for predicting HBsAg loss.Fil: Fainboim, Hugo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Di Benedetto, Nicolas. Hospital Arrecifes; ArgentinaFil: Paz, Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Mendizabal, Manuel. Universidad Austral; ArgentinaFil: Campuzano, Soledad. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Elizalde, Maria Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Tadey, Luciana. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Deluchi, Gabriel. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Bouzas, María Belén. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Mammana, Lilia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Flichman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

HLA-Driven Convergence of HIV-1 Viral Subtypes B and F Toward the Adaptation to Immune Responses in Human Populations

BACKGROUND: Cytotoxic T-Lymphocyte (CTL) response drives the evolution of HIV-1 at a host-level by selecting HLA-restricted escape mutations. Dissecting the dynamics of these escape mutations at a population-level would help to understand how HLA-mediated selection drives the evolution of HIV-1. METHODOLOGY/PRINCIPAL FINDINGS: We undertook a study of the dynamics of HIV-1 CTL-escape mutations by analyzing through statistical approaches and phylogenetic methods the viral gene gag sequenced in plasma samples collected between the years 1987 and 2006 from 302 drug-naive HIV-positive patients. By applying logistic regression models and after performing correction for multiple test, we identified 22 potential CTL-escape mutations (p-value<0.05; q-value<0.2); 10 of these associations were confirmed in samples biologically independent by a Bayesian Markov Chain Monte-Carlo method. Analyzing their prevalence back in time we found that escape mutations that are the consensus residue in samples collected after 2003 have actually significantly increased in time in one of either B or F subtype until becoming the most frequent residue, while dominating the other viral subtype. Their estimated prevalence in the viral subtype they did not dominate was lower than 30% for the majority of samples collected at the end of the 80's. In addition, when screening the entire viral region, we found that the 75% of positions significantly changing in time (p<0.05) were located within known CTL epitopes. CONCLUSIONS: Across HIV Gag protein, the rise of polymorphisms from independent origin during the last twenty years of epidemic in our setting was related to an association with an HLA allele. The fact that these mutations accumulated in one of either B or F subtypes have also dominated the other subtype shows how this selection might be causing a convergence of viral subtypes to variants which are more likely to evade the immune response of the population where they circulate

HUMAN HERPESVIRUS 8 CAN BE TRANSMITTED THROUGH BLOOD IN DRUG ADDICTS

Human Herpes virus type-8 (HHV-8) seroprevalence was studied in a population of HIV positive intravenous drug users (IVDUs) from Argentina. Analysis of this population also indirectly made it possible to study HHV-8 blood transmission, because these individuals frequently engage in needle sharing behavior and are capable of acquiring a broad array of blood borne pathogens, including Hepatitis B/C virus. The seroprevalence of HHV-8 in IVDUs was compared to a group of non-IVDUs and HIV negative individuals. Of the 223 individuals tested, 13.45% were HHV-8 positive, 16.99% in the IVDUs group, and 5.71% in the non-IVDUs. Among HIV positive IVDUs, 25/144 (17.36%) were also HHV-8 seropositive. The seropositivity rate of HHV-8 in HIV negative IVDUs was 11.1%. In contrast, HHV-8 seroprevalence in HIV negative heterosexual individuals without drug usage behavior was even lower (5.71%). The rate of HHV-8 infection in HIV positive IVDUs was three times as high compared to the non IVDU HIV negative individuals, suggesting that IVDU is a risk for HHV-8 infection. Furthermore, it was found that IVDUs showed a very high rate of Hepatitis B/C (52.77%), which also correlate with HHV-8 infection in this population (23.68%). All Hepatitis B/C positive individuals were also HIV positive. Our data confirm other studies showing that individuals who share needles are at risk for acquiring Hepatitis B/C and HIV infections. In addition, our results suggest that they are also at risk to acquiring HHV-8 infection by the same route