Long-term hepatitis B virus dynamics in HIV-hepatitis B virus-co-infected patients treated with tenofovir disoproxil fumarate.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Lacombe
Karine
K
Inserm U707, Université Pierre et Marie Curie, 27 rue de Chaligny, 75571 Paris cedex 12, France. karine.lacombe@sat.aphp.fr
Gozlan
Joël
J
Boelle
Pierre-Yves
PY
Serfaty
Lawrence
L
Zoulim
Fabien
F
Valleron
Alain-Jacques
AJ
Girard
Pierre-Marie
PM
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D004279:DNA, Viral / Q000097:blood; D004812:Epidemiologic Methods; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006515:Hepatitis B virus / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D000068698:Tenofovir; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D004279:DNA, Viral; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine