By Liz Highleyman

CD4 T-cells play a key role in response to many pathogens, but their contribution to fighting hepatitis B virus (HBV) are not fully understood.

In a study presented at the recent 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008) in San Francisco, researchers looked at the influence of CD4 cell count on HBV viral load decline during treatment with adefovir (Hepsera).

Coinfection with HIV and HBV substantially alters the natural course of HBV infection, as well as its management, the investigators noted as background. Directly targeted anti-HBV agents -- including adefovir, lamivudine (Epivir-HBV), entecavir (Baraclude), telbivudine (Tyzeka), and tenofovir (Viread) -- effectively suppress HBV DNA, but the kinetics of viral decline and the factors that predict it have not yet been clearly established.

In the present double-blind, randomized study, the researchers evaluated HBV viral kinetics during adefovir therapy in lamivudine-resistant HIV positive (n=12) and HIV negative (n=5) chronic hepatitis B patients. All 5 HIV negative participants received adefovir, while the HIV-HBV coinfected patients were randomly assigned to receive either adefovir (n=8) or placebo (n=4) for a total of 48 weeks. After 48 weeks, all participants received open-label adefovir for an additional 48 weeks.

HBV and HIV viral loads were measured on days 0, 1, 3, 5, 7, 10, 14, and 28, and then every 4 weeks. Immune profiles, liver chemistry, and laboratory safety evaluations were performed at baseline and on an ongoing basis after starting treatment.

Results

• HIV-HBV coinfected patients receiving adefovir demonstrated a significantly lower decline in HBV DNA compared with HBV monoinfected patients:

• Week 4: median -2.54 vs -3.52 log (P < 0.03);

• End of treatment: median -5.37 vs -7.00 log (P < 0.03).

• Adefovir pharmacokinetics was similar in the HIV positive and HIV negative groups (P > 0.5).

• Baseline CD4 cell counts correlated positively with the second-slope decline of HBV in all patients (R = 0.8; P < 0.001), particularly coinfected individuals (R = 0.65; P < 0.05).

• HIV-HBV coinfected patients with a CD4 count < 600 cells/mm3 had a much smaller HBV viral load decline than those with > 600 cells/mm3 (P < 0.05).

Based on these findings, the investigators concluded, "HIV coinfection status is associated with lower HBV viral response rates to adefovir."

"Baseline CD4+ T-cell count is an independent predictor of HBV decline in both HIV positive and HIV negative subjects, emphasizing the role of immune status on clearance of HBV-infected hepatocytes," they continued.

However, they added, "the pharmacokinetics of adefovir was not affected by HIV serostatus and did not predict HBV viral response in [either] HIV negative [or] HIV positive subjects."

The researchers said they plan to conduct future studies focused on evaluating the relationship between baseline CD4 T-cell count and long-term HBV suppression.

12/5/08

Reference
E Formentini, AU Neumann, MG Ghany, and others. Baseline CD4+ T Cell Count Predicts HBV Decline in HIV Negative and Positive and Patients Treated with Adefovir Dipivoxil. 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008). San Francisco. October 31-November 4, 2008. Abstract 954.