Combination of tenofovir and lamivudine versus tenofovir after lamivudine failure for therapy of hepatitis B in HIV-coinfection.
OBJECTIVE
At present sequential monotherapy for chronic hepatitis B with hepatitis B virus (HBV)-polymerase inhibitors is clinical practice. It is unknown to date whether combination therapy with lamivudine plus tenofovir could be superior to sequential therapy with tenofovir after the occurrence of lamivudine resistance.


METHODS
We conducted a multicenter, 1: 2 matched pair analysis comparing patients with HBV/HIV-coinfection starting an antiretroviral regimen including tenofovir plus lamivudine with patients who had highly replicative, lamivudine resistant HBe-antigen positive chronic hepatitis B and started with tenofovir as the only active HBV polymerase inhibitor subsequent to lamivudine.


RESULTS
At baseline patients on tenofovir plus lamivudine (n = 25) had a median HBV DNA of 5.9 x 10(7) copies/ml compared to 1.37 x 10(8) copies/ml in the tenofovir arm (n = 50; P = 0.32). A sustained undetectable HBV DNA < 1000 copies/ml was achieved in 19/25 (76%) patients on tenofovir plus lamivudine and in 42/50 (84%) on tenofovir (P = 0.53). A loss of HBe-antigen was observed in 9/25 (36%) patients on tenofovir plus lamivudine and in 12/50 (24%) patients on tenofovir (P = 0.29). HBs-antigen loss was found in 1/25 (4%) and 3/50 (6%) patients.


CONCLUSIONS
In this cohort of HBV/HIV-coinfected individuals, full HBV DNA suppression was achieved in the majority of patients independent of treatment allocation. Loss of HBe- and HBs-antigen was not different between the two study arms. Over a median treatment period of 116 weeks tenofovir was as effective as tenofovir plus lamivudine. Longer treatment periods may be needed to evaluate potential benefits of first-line combination therapy for chronic hepatitis B.
Schmutz
Guenther
G
Center for HIV and Hepatogastroenterology, Grafenberger Allee 128a, 40237 Duesseldorf, Germany.
Nelson
Mark
M
Lutz
Thomas
T
Sheldon
Julie
J
Bruno
Raffaele
R
von Boemmel
Florian
F
Hoffmann
Christian
C
Rockstroh
Juergen
J
Stoehr
Albrecht
A
Wolf
Eva
E
Soriano
Vincent
V
Berger
Florian
F
Berg
Thomas
T
Carlebach
Amina
A
Schwarze-Zander
Carolynne
C
Schürmann
Dirk
D
Jaeger
Hans
H
Mauss
Stefan
S
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000627:therapeutic use; D016009:Chi-Square Distribution; D004279:DNA, Viral / Q000032:analysis; D024882:Drug Resistance, Viral / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D015497:HIV-1; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D063065:Organophosphonates / Q000627:therapeutic use*; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D000068698:Tenofovir; D017211:Treatment Failure
D019380:Anti-HIV Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000068698:Tenofovir; D000225:Adenine