Long-term Hepatitis B Virus (HBV) Dynamics in HIV-HBV Coinfected Patients Treated with Tenofovir

Long-term Hepatitis B Virus (HBV) Dynamics in HIV-HBV Coinfected Patients Treated with Tenofovir

Although tenofovir/ TDF (Viread) is widely regarded as a potent therapy for the treatment of chronic HBV infection, there are few studies to document its use in this capacity. Study results on the use of tenofovir for the treatment of HBV in HIV coinfection are even scarcer, especially concerning the drug’s long-term impact in this patient population.

French researchers have conducted a prospective study of HBV-DNA decay kinetics in 28 HIV-HBV-co-infected patients treated with TDF. HBV dynamics were studied using mixed linear models, and baseline factors affecting them were analyzed using Cox models. Following are the results of this study, published in the current online issue of AIDS (June 10, 2005).

Results

·         HBV-DNA load declined by a mean of 4.6 log copies/ml during follow-up (mean 71 weeks), and fell below the detection limit (200 copies/ml) in 21 patients.

·         Inhibition of viral replication by TDF was associated with a decrease in alanine aminotransferase levels (125 versus 68 IU, P < 0.05).

·         HBV-DNA decay was biphasic, with a rapid fall followed by a gradual decline.

·         Baseline factors associated with a steeper first slope in the HBV-DNA decrease were high HBV load, positive hepatitis B e antigen (HBeAg) and YMDD mutations.

·         Baseline factors increasing the time to reach an HBV-DNA level less than 200 copies/ml were high HBV load (150 days when HBV-DNA < 108 log, 316 days when HBV-DNA > 108 log) and positive HBeAg.

·         Previous exposure to lamivudine or TDF-lamivudine did not modify HBV-DNA decrease under therapy in this population with a high prevalence of YMDD mutations.

Based on these results, the French authors conclude, “The long-term decline in HBV DNA under TDF is biphasic and is primarily influenced by the initial HBV load.”

Furthermore, they note, “The clinical significance of such an association remains moderate, and TDF can be efficiently included in the highly active antiretroviral therapy regimen of HIV-HBV-co-infected patients, regardless of HBV strains and their degree of replication.”

Discussion

Most of the patients studied had been exposed to lamivudine (Epivir-HBV), and the HBV strain was often resistant to this drug. The mean decline in HBV viral load was 4.6 log copies/ml after 71 weeks of TDF therapy, in keeping with the results of a recent clinical trial (-4.5 log at 48 weeks in pretreated patients).

HBV-DNA PCR became undetectable in 75% of patients (including all the HBeAg-negative patients), and 16.7% of patients who were HBeAg-positive patients seroconverted to hepatitis B e antibodies.

These results confirm, with longer follow-up, the activity of TDF on HBV in HIV-HBV co-infection, even in patients with lamivudine-resistant or presumed pre-C mutant strains. This antiviral activity also had a marked impact on liver function, as ALT activity fell significantly in all 28 patients studied.

Concerning TDF tolerability, no grade III or more adverse events occurred. Creatinemia increased slightly in the treated patients but none developed severe renal impairment. This is in keeping with the results of previous clinical trials, although cases of Fanconi syndrome in patients regularly followed in HIV clinics have been published.

Hepatitis B Viral Dynamics

The factor most strongly associated with a longer time to undetectability is the initial HBV viral load. This result might have a clinical impact because a twofold difference in initial HBV load leads to a difference of one week in the loss of one log of viral load.

The investigators also found that the slope of the first decay phase was steeper when the baseline HBV viral load was high. The explanation for this unexpected result probably relies on intrahepatic events such as the kinetics of the death of infected hepatocytes or the efficacy of local immune responses.

Finally, the authors conclude, “Overall, in this prospective study of 28 pretreated HIV-HBV-co-infected patients, TDF had a potent and durable effect on HBV replication in all patients despite the viral diversity of the HBV strains. Larger prospective studies are needed to determine the precise impact of HIV-induced immunodeficiency and HBV genomic variability on the response to TDF.”

From the Inserm U707, Université Pierre et Marie Curie, Paris, France, Service d'Hépato-gastro-entérologie, Hôpital Saint-Antoine, Paris, France, and^fUnité Inserm 271, Institut Universitaire de France, Lyon, France.

        HIV-HBV Coinfection
        Conference Coverage

Treatment and Management of
  HBV-HIV Coinfection:
  The Goals of Therapy for HBV
   April 2005

1st European Conference on the
Treatment of HBV and HCV in
HIV Co-infected Patients
  March 2005

More Articles on Treatment for HIV-HBV Coinfection

Articles on Tenofovir in HIV infection

05/25/05

Reference
K Lacombe and others. Long-term hepatitis B virus dynamics in HIV-hepatitis B virus-co-infected patients treated with tenofovir disoproxil fumarate. AIDS 19(9): 907-915. June 10, 2005.