No Increase in Hepatitis B Virus (HBV)-Specific CD8 + T Cells in Patients with HIV-1-HBV Coinfections following HBV-Active Highly Active Antiretroviral Therapy

Abstract

ABSTRACT Following treatment of hepatitis B virus (HBV) monoinfection, HBV-specific T-cell responses increase significantly; however, little is known about the recovery of HBV-specific T-cell responses following HBV-active highly active antiretroviral therapy (HAART) in HIV-HBV coinfected patients. HIV-HBV coinfected patients who were treatment naïve and initiating HBV-active HAART were recruited as part of a prospective cohort study in Thailand and followed for 48 weeks ( n = 24). Production of gamma interferon (IFN-γ) and tumor necrosis factor α (TNF-α) in both HBV- and HIV-specific CD8 + T cells was quantified using intracellular cytokine staining on whole blood. Following HBV-active HAART, the median (interquartile range) log decline from week 0 to week 48 for HBV DNA was 5.8 log (range, 3.4 to 6.7) IU/ml, and for HIV RNA it was 3.1 (range, 2.9 to 3.5) log copies/ml ( P < 0.001 for both). The frequency of HIV Gag-specific CD8 + T-cell responses significantly decreased (IFN-γ, P < 0.001; TNF-α, P = 0.05). In contrast, there was no significant change in the frequency (IFN-γ, P = 0.21; TNF-α, P = 0.61; and IFN-γ and TNF-α, P = 0.11) or magnitude (IFN-γ, P = 0.13; TNF-α, P = 0.13; and IFN-γ and TNF-α, P = 0.13) of HBV-specific CD8 + T-cell responses over 48 weeks of HBV-active HAART. Of the 14 individuals who were HBV e antigen (HBeAg) positive, 5/14 (36%) lost HBeAg during the 48 weeks of follow-up. HBV-specific CD8 + T cells were detected in 4/5 (80%) of patients prior to HBeAg loss. Results from this study show no sustained change in the HBV-specific CD8 + T-cell response following HBV-active HAART. These findings may have implications for the duration of treatment of HBV in HIV-HBV coinfected patients, particularly in HBeAg-positive disease.