Predictors of hepatitis B virus genotype and viraemia in HIV-infected patients with chronic hepatitis B in Europe

Abstract

Background: Both natural history and treatment outcome of hepatitis B virus (HBV) infection are influenced by genotypes and viral load. Information about factors determining HBV genotype distribution and viraemia in HIV/HBV-co-infected patients is scarce.Methods: All HIV-positive patients living in Europe and Argentina recruited in EuroSIDA (1994EuroSIDA ( -2006 were tested for serum HBV surface antigen (HBsAg). Chronic carriers were further characterized virologically at one central laboratory. Variables influencing HBV genotype distribution and viraemia were assessed using logistic regression.Results: From 16 505 HIV patients enrolled in EuroSIDA, 1179 (7.1%) were HBsAg positive, of whom 474 had specimens that allowed inclusion in the virological substudy. Overall 293 (62%) were treated with anti-HBV active antiretroviral drugs at the time of testing. Hepatitis delta virus superinfection was recognized in 14% and hepatitis C virus (HCV) antibodies in 27%. Serum HBV DNA was detectable in 315 (66.5%) and HBV genotyping gave results in 170 (35.9%) patients. HBV genotype distribution was as follows: A (72.9%), D (17.1%), G (1.8%), E (1.2%), F (1.2%) and C (0.6%); another 5.9% were co-infected with multiple HBV genotypes. In the multivariate analysis, the best predictor of HBV genotype A infection was risk exposure other than intravenous drug use, whereas predictors for detectable HBV viraemia were lower CD4 counts and lack of HCV antibodies. Conclusion:A substantial proportion of HIV-positive patients with chronic hepatitis B show detectable HBV viraemia despite being treated with anti-HBV active antiretroviral drugs (mainly lamivudine). Low CD4 counts were associated with an independent higher risk of detectable HBV viraemia, which supports an earlier introduction of antiretroviral therapy, including anti-HBV drug(s) more potent than lamivudine.

Management and treatment of chronic hepatitis B virus infection in HIV positive and negative patients: The EPIB 2008 study

“…This shows that wild-type HBV seems to remain particularly frequent in the setting of HIV infection, which is not the case in HBV mono-infected patients. As HBV assessment becomes more frequent, it appears that the HBV genotype is often type A in HIV positive patients, as previously observed [4,14], which is not the case in HIV negative ones (where the D genotype prevails). This probably reflects the difference between HIV positive and HIV negative patients concerning geographic origin [15].…”

“…In most Western countries, chronic hepatitis B (CHB) is frequently associated with HIV infection, with a 5-to 10-fold greater prevalence compared to the non HIV population, since 5% to 10% of HIV positive patients are chronically infected with HBV [1][2][3][4]. The impact and the perception of HBV-HIV co-infection have evolved over time, from a negligible problem overshadowed by the AIDS related illnesses, towards a genuine risk factor for increased morbidity and mortality [2,5].…”

Outbreak of Infections by Hepatitis B Virus Genotype A and Transmission of Genetic Drug Resistance in Patients Coinfected with HIV-1 in Japan

“…Interestingly, predominant genotype A HBV coinfection in HIV-seropositive MSM populations has also been reported in European and South American countries (20,26,33), suggesting that the prevailing genotype A in HIV-seropositive MSM has become a worldwide HBV epidemic. Regarding HBV genotypes in the HIV-negative population in Japan, genotype A has been increasing, but the major HBV genotype is still C, with genotype A remaining at 3.5% nationwide and 2.1% in the Tokai area, which includes Nagoya city (9).…”

Improved Immune Status Corresponds with Long-Term Decline of Quantitative Serum Hepatitis B Surface Antigen in HBV/HIV Co-infected Patients

“…A reduction and even elimination of HBsAg is thought to occur mainly by the immune-mediated clearance of HBV-infected cells, rather than by nucleoside-analogue-induced inhibition of the viral polymerase, supporting the importance of a competent immune system for viral control (5). The negative effect of low CD4 counts on HBV-related parameters could be shown previously in HBV/HIV co-infected patients, in whom it was associated with detectable HBV viremia (20). Patients with a final CD4 count > 350 cells/lL also had a more pronounced HBsAg decline.…”

“…Also, patients showing rapid on-treatment HBsAg declines are more likely to achieve serological end-points like HBeAg seroconversion or HBsAg loss, and virological endpoints including sustained viral suppression. While it could be shown that low CD4 counts are a risk factor for the persistence of HBV-DNA in HBV/HIV-co-infected subjects (3,12), data on quantitative HBsAg in special cohorts are scarce, and could help identify the parameters associated with HBsAg declines (14,20,21). Here the longitudinal course of HBsAg in 51 HBV/HIV co-infected patients followed for a mean of approximately 3.5 y is reported.…”