The recombinant Hepatitis B surface antigen vaccine inadequately protects those living with HIV from Hepatitis B virus infection. This study utilized saved serum samples from a retrospective cohort of persons with HIV and documented vaccine-induced HBsAb seroconversion to determine factors associated with persistence of protective levels of HBsAb (≥10mIU/ml). HBsAb levels fell below 10mIU/ml in 27% of the cohort after a median follow-up of 43 months. HIV viral load suppression (<50copies/ml) at the time of vaccination was the major factor associated with persistence of protective levels of HBsAb (OR 3.83, p <0.01). Among individuals who lost protective levels of HBsAb, booster doses of vaccine re-instated the development of protective levels of HBsAb. Delaying or repeating HBV vaccination until after suppression of HIV viral load is achieved should be considered HBV antibody levels should be followed over time and boosters given with loss of protective levels of HBsAb.

The recombinant Hepatitis B surface antigen vaccine inadequately protects those living with HIV from Hepatitis B virus infection. This study utilized saved serum samples from a retrospective cohort of persons with HIV and documented vaccine-induced HBsAb seroconversion to determine factors associated with persistence of protective levels of HBsAb (≥10mIU/ml). HBsAb levels fell below 10mIU/ml in 27% of the cohort after a median follow-up of 43 months. HIV viral load suppression (<50copies/ml) at the time of vaccination was the major factor associated with persistence of protective levels of HBsAb (OR 3.83, p <0.01). Among individuals who lost protective levels of HBsAb, booster doses of vaccine re-instated the development of protective levels of HBsAb. Delaying or repeating HBV vaccination until after suppression of HIV viral load is achieved should be considered HBV antibody levels should be followed over time and boosters given with loss of protective levels of HBsAb.

Objetivo : Determinar los factores de riesgo asociados a la transmisión del virus de la Hepatitis B (VHB) en el Centro Médico Naval durante el período de estudio. Material y métodos : Estudio de casos y controles. Se evaluaron los pacientes hospitalizados en la Sala de Enfermedades Transmisibles con el diagnóstico de Síndrome ictérico mas hipertransaminasemia ( TGO y/o TGP > 500 u/l ). Los factores de riesgo reportados entre los sujetos infectados con el VHB (B+); fueron comparados con los sujetos no infectados (B-), mediante el análisis bivariado y multivariado. Resultados : Un total de 74 sujetos fueron evaluados serológicamente para VHB, de los cuales 37 fueron positivos ( 35 infección aguda y 2 infección no aguda ). Los sujetos B+ fueron en su mayoría de sexo masculino y tuvieron como factor de riesgo mas significativo una hospitalización previa ( OR:13.33 ). Además se describen los cuadros clínicos y exámenes de laboratorio encontrados en ambos grupos. Conclusión : La fuerte asociación encontrada entre hepatitis B y hospitalización previa, sugiere que la transmisión horizontal nosocomial tiene un rol protagónico en la transmisión del VHB en el Centro Médico Naval.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Medicine / Master / Doctor of Medicine

No description available.

Hepatitis B virus genotype G (HBV/G) is a unique genotype of HBV which contains a 36-nucleotide insertion in the Core gene as well as 2 mutations that lead to stop codons in the Pre-Core coding region. Chronic infection with HBV/G is not known to occur without a co-infecting HBV genotype, suggesting that it is defective on its own. This study aims to look at the replication capacity of HBV/G, HBV/A, and HBV/A/G recombinant strains circulating in Canada and to determine the relationship between co-infecting strains. Four full-length HBV genomes were isolated from 2 different patients and transiently transfected into the HepG2 human hepatoma cell line for phenotypic analysis of each strain. HBV/G, HBV/A and HBV/A/G recombinant strains were isolated from Patient 1, while a different HBV/A/G recombinant strain was isolated from Patient 2. HBV replication capacity was measured using a quantitative real time PCR assay. Markers of replication, such as secreted HBsAg and HBeAg, intracellular core particles and replicative DNA intermediates were measured by ELISA, Western blot and Southern blot, respectively. HBV/G demonstrated a higher replicative capability, relative to its co-infecting strains, while both HBV/A/G strains had levels of secreted HBV DNA greater than HBV/A alone, suggesting a modulating effect due to recombination. Replication marker levels revealed possible reasons for a co-infection requirement during HBV/G infection such as HBeAg for chronicity. These observations demonstrate the potential interactions of HBV/G with its co-infecting HBV genotype and provide the first reported phenotypic analysis of a HBV recombinant.

In 2010, the Hepatitis B virus (HBV) infected 1.2 million people in the United States, many of whom were unaware of their infection (CDC, 2010). The available research on HBV infection is predominately among Asian American, Native Hawaiian, and other Pacific Islander. HBV infection and Human Immunodeficiency Virus (HIV) infection share similar modes of transmission. Very little HBV research has been dedicated to the African American females; who accounted for 29% of the new HIV cases among young adolescents in 2010 (CDC, 2010). Due to the common mode of transmission of HIV and Hepatitis B many persons at risk for HIV are also at risk for contracting Hepatitis B. One’s risk for acquisition of HBV can be mitigated or eliminated by vaccination or naturally acquired immunity. In the absence of both, an individual is susceptible to acquisition of HBV. The aims of this study are to define susceptibility of non-Hispanic, blacks to Hepatitis B infection compared to other races as well as defining possible risk factors that may increase or decrease their susceptibility.

Hepatitis B virus genotype G (HBV/G) is a unique genotype of HBV which contains a 36-nucleotide insertion in the Core gene as well as 2 mutations that lead to stop codons in the Pre-Core coding region. Chronic infection with HBV/G is not known to occur without a co-infecting HBV genotype, suggesting that it is defective on its own. This study aims to look at the replication capacity of HBV/G, HBV/A, and HBV/A/G recombinant strains circulating in Canada and to determine the relationship between co-infecting strains. Four full-length HBV genomes were isolated from 2 different patients and transiently transfected into the HepG2 human hepatoma cell line for phenotypic analysis of each strain. HBV/G, HBV/A and HBV/A/G recombinant strains were isolated from Patient 1, while a different HBV/A/G recombinant strain was isolated from Patient 2. HBV replication capacity was measured using a quantitative real time PCR assay. Markers of replication, such as secreted HBsAg and HBeAg, intracellular core particles and replicative DNA intermediates were measured by ELISA, Western blot and Southern blot, respectively. HBV/G demonstrated a higher replicative capability, relative to its co-infecting strains, while both HBV/A/G strains had levels of secreted HBV DNA greater than HBV/A alone, suggesting a modulating effect due to recombination. Replication marker levels revealed possible reasons for a co-infection requirement during HBV/G infection such as HBeAg for chronicity. These observations demonstrate the potential interactions of HBV/G with its co-infecting HBV genotype and provide the first reported phenotypic analysis of a HBV recombinant.

The viral dynamics of the hepatitis C virus (HCV) in newly acquired infection are not well understood. HCV exists within an individual as a spectrum of minor variants termed quasispecies. The evolution of minor variants may contribute to viral escape of the host?s immune response, thereby facilitating development of chronic infection. The hypervariable 1 region (HVR1) is the most heterogeneous part of the HCV genome and contains a putative B-cell epitope. Thus, diversity in HVR1 could be a strategy used to evade neutralising antibodies. Acutely infected individuals (n=24) were examined with the aim of defining HVR1 quasispecies diversity in acute infection. The characterisation of the E1/HVR1 sequence and host specific evolution of HCV minor variants in treatment nonresponders was also investigated. HCV E1/HVR1 fragments were amplified from 48 sera using a combined reverse transcription-polymerase chain reaction (RT-PCR). Products were TA cloned into pCRIITOPO and approximately 10-20 clones were sequenced from each sample. HVR1 quasispecies diversity was examined longitudinally via sequence analysis. Quasispecies diversity was characterised primarily by mean nucleotide diversity. The mean HVR1 diversity of the acute cohort (n=48; 2.12% ?? 2.22) was lower than the diversity obtained for a cohort of chronically infected individuals (n=99; 4.5% ?? 5.1). There was no significant difference in mean HVR1 diversity between the HIV/HCV co-infected and HCV mono-infected groups (p=0.99) or between the clearer and non-clearer groups (p=0.85). Examination of amino acid usage and the hydropathic profile of each position in HVR1 revealed that sequence variation was confined to specific sites. The investigation of host specific evolution of HVR1 quasispecies demonstrated that minor variants (comprising 10- 20% of a population) became the dominant species over time in two treatment non-responders. These variants bore mutations that were not reflected in the consensus sequence of their respective populations at the initial timepoint analysed. Common infection was identified by 98% HVR1 sequence homology within two pairs of individuals. The evolution of common strains appeared to be different between individuals, suggesting host pressures may influence quasispecies evolution. This thesis provided an insight into the viral dynamics and host specific evolution of acute phase quasispecies.