Background:  HIV-1/hepatitis B virus (HBV) co-infection significantly alters the natural history of HBV infection. Generation of HBV-specific immunity is important for a sustained response to anti-HBV therapy but may be impaired in the setting of HIV/HBV co-infection.

Methods:  Peripheral blood from HIV/HBV co-infected individuals (n = 28) was analyzed pre-HAART and 4, 12, 24, and 48 weeks following initiation of HBV-active HAART in Bangkok, Thailand. Patients were randomized to receive either tenofovir (TDF), lamivudine (3TC), TDF/3TC or TDF/emtricitabine (FTC) within an efavirenz (EFV) -based HAART regimen. Blood from each time-point was stimulated with HBV (whole genome) or HIV (gag) overlapping peptide pools and interferon (IFN) -g and tumor necrosis factor (TNF) -a production was assessed by intracellular cytokine staining. Only CD8⁺ T cell responses could be assessed given the low CD4 count prior to HAART (median 60 cells/µL).

Results:  After 48 weeks of HAART, the proportion of individuals with undetectable HBV viral load (<358 IU/mL) was 76% and HIV viral load (<50 copies/mL) was 100%. HBeAg⁺ individuals (n = 16) had a significantly higher HBV viral load than HBeAg^– individuals (n = 12) pre-HAART (p = 0.020) and following 48 weeks of HAART (p = 0.021). After 8 weeks of HAART, alanine aminotransferase (ALT) was significantly lower in HBeAg⁺ patients compared to HBeAg^- patients (p = 0.034). Both the frequency of responders and magnitude of HIV gag-specific CD8⁺ T cells progressively decreased following HAART in all patients, as has been previously documented. There was no significant change in the frequency of HBV-specific CD8⁺ T cell responders over the 48 weeks of HAART (mean frequency of responders = 27% at week 0 and 18% at week 48). There was however a transient increase in the magnitude of the HBV-specific IFN-g⁺ and TNF-α⁺ CD8⁺ T cell response in the first 12 weeks of HAART which was most prominent for the TNF-α⁺ CD8⁺ T cell response in HBeAg⁺ individuals (mean magnitude of response at 0, 12, and 48 weeks was 0.02%, 0.24%, 0.03%, respectively). By 48 weeks there was no difference in the magnitude of the HBV-specific CD8⁺ T cell response compared to pre-HAART samples. There was no correlation between the magnitude of HBV-specific CD8⁺ T cell responses and ALT, HBV viral load, or CD4 count either prior to or following HAART.

Conclusions:  In HIV/HBV co-infection, there is only a transient increase in HBV-specific CD8⁺ T cells despite successful virological control of both HIV and HBV. This may have implications for the optimal duration of HBV-active HAART particularly in HBeAg^– individuals.