Patterns and causes of suboptimal response to tenofovir-based therapy in individuals coinfected with HIV and hepatitis B virus

Abstract

Background: Tenofovir (TDF) is effective for treatment of hepatitis B virus (HBV) in human immunodeficiency virus (HIV) infection; however, some individuals have ongoing HBV viremia, the reasons for which are unclear. We determined the patterns and factors associated with detectable HBV DNA in HIV-HBV-coinfected subjects on highly active antiretroviral therapy (HAART).

Methods: One hundred sixty-five HIV-HBV-coinfected individuals from the United States, Australia, and Thailand, the majority of whom were on HAART at study entry, were prospectively followed semiannually for a median of 2.8 years. Logistic regression was used to determine factors associated with detectable HBV DNA.

Results: Anti-HBV regimens were TDF/emtricitabine (57%), lamivudine or emtricitabine (19%), or TDF monotherapy (13%). During follow-up, HBV DNA was detected at 21% of study visits and was independently associated with hepatitis B e antigen (HBeAg), HAART <2 years, CD4 <200 cells/mm(3), detectable HIV RNA, reporting <95% adherence, and anti-HBV regimen. TDF/emtricitabine was less likely to be associated with detectable HBV than other regimens, including TDF monotherapy (odds ratio, 2.79; P = .02). In subjects on optimal anti-HBV therapy (TDF/emtricitabine) and with undetectable HIV RNA, HBeAg, CD4 <200 mm(3), and reporting <95% adherence remained associated with detectable HBV DNA. Three main patterns of HBV viremia were observed: persistent HBV viremia, viral rebound (>1 log from nadir), and viral blips. No TDF resistance was identified.

Conclusions: Tenofovir/emtricitabine was superior to other anti-HBV regimens in long-term HBV suppression. HBV viremia on therapy was identified in 1 of 3 main patterns. Suboptimal adherence was associated with detectable HBV DNA during therapy, even when HIV was undetectable.

Figure 1.

Proportion of individuals coinfected with human immunodeficiency virus and hepatitis B virus (HBV) with undetectable HBV DNA by HBV active regimen. Abbreviations: FTC, emtricitabine; LMV, lamivudine; TDF, tenofovir.

Figure 2.

Patterns of suboptimal response in tenofovir-treated individuals. A, Persistent viremic pattern. B, Hepatitis B virus (HBV) rebound. C, Viral blip. Dotted line = lower limit of detection of HBV DNA. Shaded box = lower limit of detection of human immunodeficiency virus (HIV) RNA. Primary y-axis: HBV DNA log₁₀ IU/mL; secondary y-axis: HIV RNA log₁₀ copies/mL; x-axis: month of study visit after cohort entry. Abbreviations: c, copies; HBV, hepatitis B virus; HIV, human immunodeficiency virus.