Doherty Institute - Research Publications
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ItemNo Preview AvailableEffects of long-term tenofovir-based combination antiretroviral therapy in HIV-hepatitis B virus coinfection on persistent hepatitis B virus viremia and the role of hepatitis B virus quasispecies diversity(LIPPINCOTT WILLIAMS & WILKINS, 2016-06-19)OBJECTIVE: Hepatitis B virus (HBV) can persist in some HIV-HBV coinfected individuals on tenofovir disoproxil fumarate (TDF)-containing combination antiretroviral therapy (cART) but HBV resistance to TDF has not been reported and the source of persistent HBV DNA on TDF is poorly understood. The aims of this study were to assess long-term HBV suppression in HIV-HBV coinfected individuals receiving TDF and investigate quasispecies variation using ultradeep pyrosequencing (UDPS). METHODS: Ninety-two HIV-HBV coinfected participants on, or about to commence, TDF-containing cART were enrolled [Australia (n = 40), Thailand (n = 52)] and followed for 2 years with study visits every 6 months. HBV reverse transcriptase sequencing was performed on samples with HBV DNA more than 400 IU/ml by population-based methods and UDPS. Quasispecies diversity was assessed using Shannon entropy. RESULTS: Over 24 months, viremia was detected at least once in 17% (n = 16) of the cohort. Novel mutations were not identified in on TDF samples tested by population-based sequencing (n = 19). Using UDPS, the median Shannon entropy value in samples prior to TDF in patients aviremic on TDF was not statistically different from those who were viremic on TDF (n = 50; 8.4 and 9.1, respectively, P = 0.9). Longitudinal Shannon entropy analysis of on TDF samples from five participants showed three individuals with significant changes in viral diversity over time. CONCLUSION: Persistent viremia on TDF-containing cART is common but TDF-resistance was not detected. In some individuals, changes in viral diversity over time were observed on TDF which could potentially be active viral replication. Further follow-up will be needed to determine the clinical significance of detectable HBV DNA on TDF-containing cART.
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ItemA gathering storm: HIV infection and nonalcoholic fatty liver disease in low and middle-income countries(LIPPINCOTT WILLIAMS & WILKINS, 2019-06-01): Despite the decreasing total incidence of liver-related deaths, liver disease remains one of the major non-AIDS causes of morbidity and mortality amongst people living with HIV, and a significant proportion of liver disease in these individuals can be attributed to nonalcoholic fatty liver disease (NAFLD). NAFLD in HIV infection is a growing problem in view of increasing life expectancy associated with the use of effective antiretroviral therapy (ART), wider uptake of ART and increasing rates of obesity in many Asian as well as western countries. The problem may be more pronounced in developing countries where there are limited resources available for mass screening and diagnosis of NAFLD. There is a small but growing body of literature examining NAFLD in the setting of HIV, with data from low and middle-income countries (LMICs) particularly lacking. Here, we review the cohort data on NAFLD in HIV, and discuss the risk factors, pathogenesis of hepatic steatosis, NAFLD and nonalcoholic steatohepatitis (NASH), diagnostic approaches and therapeutic options available for NAFLD in the setting of HIV, and the specific challenges of NAFLD in HIV for LMICs.
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ItemLiver Fibrosis Regression Measured by Transient Elastography in Human Immunodeficiency Virus (HIV)-Hepatitis B Virus (HBV)-Coinfected Individuals on Long-Term HBV-Active Combination Antiretroviral Therapy(OXFORD UNIV PRESS INC, 2016-01)Background. Advanced fibrosis occurs more commonly in human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfected individuals; therefore, fibrosis monitoring is important in this population. However, transient elastography (TE) data in HIV-HBV coinfection are lacking. We aimed to assess liver fibrosis using TE in a cross-sectional study of HIV-HBV coinfected individuals receiving combination HBV-active (lamivudine and/or tenofovir/tenofovir-emtricitabine) antiretroviral therapy, identify factors associated with advanced fibrosis, and examine change in fibrosis in those with >1 TE assessment. Methods. We assessed liver fibrosis in 70 HIV-HBV coinfected individuals on HBV-active combination antiretroviral therapy (cART). Change in fibrosis over time was examined in a subset with more than 1 TE result (n = 49). Clinical and laboratory variables at the time of the first TE were collected, and associations with advanced fibrosis (≥F3, Metavir scoring system) and fibrosis regression (of least 1 stage) were examined. Results. The majority of the cohort (64%) had mild to moderate fibrosis at the time of the first TE, and we identified alanine transaminase, platelets, and detectable HIV ribonucleic acid as associated with advanced liver fibrosis. Alanine transaminase and platelets remained independently advanced in multivariate modeling. More than 28% of those with >1 TE subsequently showed liver fibrosis regression, and higher baseline HBV deoxyribonucleic acid was associated with regression. Prevalence of advanced fibrosis (≥F3) decreased 12.3% (32.7%-20.4%) over a median of 31 months. Conclusions. The observed fibrosis regression in this group supports the beneficial effects of cART on liver stiffness. It would be important to study a larger group of individuals with more advanced fibrosis to more definitively assess factors associated with liver fibrosis regression.
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ItemQuantitative HBsAg and HBeAg Predict Hepatitis B Seroconversion after Initiation of HAART in HIV-HBV Coinfected Individuals(PUBLIC LIBRARY SCIENCE, 2013-04-09)OBJECTIVE: Anti-HBe seroconversion and HBsAg loss are important therapeutic endpoints in patients with hepatitis B virus (HBV) infection. Quantitative measures of hepatitis B surface antigen (qHBsAg) and e antigen (qHBeAg) have been identified as potentially useful indicators of therapeutic response in HBV monoinfection. The aim of this study was to examine serological change including quantitative biomarkers in HIV-HBV coinfected patients initiating HBV active antiretroviral therapy (ART). METHODS: HIV-HBV coinfected individuals from Thailand were followed for up to 168 weeks post ART. Rates and associations of qualitative serological change were determined. Longitudinal changes in qHBsAg and qHBeAg were measured and their utility as predictors of response examined. RESULTS: Forty seven patients were included of whom 27 (57%) were HBeAg positive at baseline. Median CD4 count was 48 cells/mm(3). Over a median follow-up of 108 weeks 48% (13/27) lost HBeAg, 12/27 (44%) achieved anti-HBe seroconversion and 13% (6/47) HBsAg loss. Anti-HBe seroconversion was associated with higher baseline ALT (p = 0.034), lower qHBsAg (p = 0.015), lower qHBeAg (p = 0.031) and greater HBV DNA decline to week 24 (p = 0.045). Sensitivity and specificity for qHBsAg and qHBeAg decline of >0.5 log at week 12 and >1.0 log at week 24 were high for both anti-HBe seroconversion and HBsAg loss. CONCLUSIONS: Rates of serological change in these HIV-HBV coinfected individuals with advanced immunodeficiency initiating HBV-active ART were high. Baseline and on treatment factors were identified that were associated with a greater likelihood of subsequent anti-HBe seroconversion, including both quantitative HBsAg and HBeAg, suggesting these biomarkers may have utility in this clinical setting.