title: 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: 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-gamma) and tumor necrosis factor alpha (TNF-alpha) 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-gamma, P < 0.001; TNF-alpha, P = 0.05). In contrast, there was no significant change in the frequency (IFN-gamma, P = 0.21; TNF-alpha, P = 0.61; and IFN-gamma and TNF-alpha, P = 0.11) or magnitude (IFN-gamma, P = 0.13; TNF-alpha, P = 0.13; and IFN-gamma and TNF-alpha, 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.
authors.affiliation: Department of Medicine, Monash University, Melbourne, Australia.
authors.forename: Megan
authors.initials: M
authors.lastname: Crane
authors.forename: Sunee
authors.initials: S
authors.lastname: Sirivichayakul
authors.forename: J Judy
authors.initials: JJ
authors.lastname: Chang
authors.forename: Anchalee
authors.initials: A
authors.lastname: Avihingsanon
authors.forename: Sasiwimol
authors.initials: S
authors.lastname: Ubolyam
authors.forename: Supranee
authors.initials: S
authors.lastname: Buranapraditkun
authors.forename: Pattarawat
authors.initials: P
authors.lastname: Thantiworasit
authors.forename: Fiona
authors.initials: F
authors.lastname: Wightman
authors.forename: Stephen
authors.initials: S
authors.lastname: Locarnini
authors.forename: Gail
authors.initials: G
authors.lastname: Matthews
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006509:Hepatitis B / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013785:Thailand