Long-term hepatitis B virus dynamics in HIV-hepatitis B virus-co-infected patients treated with tenofovir disoproxil fumarate.
ABSTRACT The long-term impact of tenofovir disoproxil fumarate (TDF) on hepatitis B virus (HBV) replication has not yet been studied in HIV-HBV-co-infected patients.
We conducted a prospective study of HBV-DNA decay kinetics in 28 HIV-HBV-co-infected patients treated by TDF. HBV dynamics were studied using mixed linear models, and baseline factors affecting them were analysed using Cox models.
The 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 an 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 < 10 log, 316 days when HBV-DNA > 10 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.
The long-term decline in HBV DNA under TDF is biphasic and is primarily influenced by the initial HBV load. However, 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.
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ABSTRACT: Tenofovir disoproxil fumarate (TDF) is an oral prodrug of tenofovir, a novel, acyclic nucleotide analogue with in vitro activity against HIV-1 and HIV-2. TDF is licensed by American Food and Drug Administration (FDA) in 2001 for the treat- ment of HIV infection. TDF is currently one of the most widely used nucleotide reverse transcriptase inhibitors (NRTIs) for the treatment of HIV infec- tion. Its efficacy, favorable toxicity profile, and convenient dosing have made this drug one of the most popular first-line treatment. Numerous stud - ies have demonstrated the use of TDF in the treat- ment of HIV infection. It also has been shown to be effective in HIV/HBV coinfected patients and in patients with wild-type and lamivudine-resistant strains. Accumulating evidence suggests that TDF is more potent in suppressing HBV replication. In this review, we summarize the study progress of TDF in treating HBV infection.
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