Abstract
BackgroundHepatitis B virus (HBV) genotypes can influence treatment outcome in HBV-monoinfected and human immunodeficiency virus (HIV)/HBV-coinfected patients. Tenofovir disoproxil fumarate (TDF) plays a pivotal role in antiretroviral therapy (ART) of HIV/HBV-coinfected patients. The influence of HBV genotypes on the response to antiviral drugs, particularly TDF, is poorly understood.MethodsHIV/HBV-co-infected participants with detectable HBV DNA prior to TDF therapy were selected from the Swiss HIV Cohort Study. HBV genotypes were identified and resistance testing was performed prior to antiviral therapy, and in patients with delayed treatment response (>6 months). The efficacy of TDF to suppress HBV (HBV DNA <20 IU/mL) and the influence of HBV genotypes were determined.Results143 HIV/HBV-coinfected participants with detectable HBV DNA were identified. The predominant HBV genotypes were A (82 patients, 57 %); and D (35 patients, 24 %); 20 patients (14 %) were infected with multiple genotypes (3 % A + D and 11 % A + G); and genotypes B, C and E were each present in two patients (1 %). TDF completely suppressed HBV DNA in 131 patients (92 %) within 6 months; and in 12 patients (8 %), HBV DNA suppression was delayed. No HBV resistance mutations to TDF were found in patients with delayed response, but all were infected with HBV genotype A (among these, 5 patients with genotype A + G), and all had previously been exposed to lamivudine.ConclusionIn HIV/HBV-coinfected patients, infection with multiple HBV genotypes was more frequent than previously reported. The large majority of patients had an undetectable HBV viral load at six months of TDF-containing ART. In patients without viral suppression, no TDF-related resistance mutations were found. The role of specific genotypes and prior lamivudine treatment in the delayed response to TDF warrant further investigation.
Highlights
Hepatitis B virus (HBV) genotypes can influence treatment outcome in HBV-monoinfected and human immunodeficiency virus (HIV)/HBV-coinfected patients
Baseline clinical characteristics were similar between the two groups with the exception of median serum alanine transaminase (ALT) levels of patients with detectable HBV DNA (slightly above normal at 47 IU/L), with no statistical differences observed between the genotypes
In the Swiss HIV Cohort study, HBV genotype A was predominant in HIV/HBVco-infected participants, followed by genotype D, which is consistent with previous reports [10, 11, 30]
Summary
Hepatitis B virus (HBV) genotypes can influence treatment outcome in HBV-monoinfected and human immunodeficiency virus (HIV)/HBV-coinfected patients. Tenofovir disoproxil fumarate (TDF) plays a pivotal role in antiretroviral therapy (ART) of HIV/HBV-coinfected patients. The influence of HBV genotypes on the response to antiviral drugs, TDF, is poorly understood. Hepatitis B virus (HBV) infection is one of the most frequent causes of end-stage liver disease. Progression of HBV-related liver disease is influenced by viral factors, such as viral load, genotype, the presence of hepatitis B e antigen (HBeAg), and the appearance of escape mutations [6,7,8,9,10,11]. Nucleos(t)ide analogues (NUCs), such as lamivudine (LAM), tenofovir disoproxil fumarate (TDF), and emtricitabine (FTC), if used as components of antiretroviral therapy (ART). Recent studies showed that these HBV-specific agents prevent liver deterioration, but can lead to seroconversion of HBeAg and even hepatitis B surface antigen
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