HIV and Hepatitis B Coinfection
K. Lacombe; A. Boyd; C. Lascoux-combe; P. Bonnard; J. Molina; P. Miailhes; L. Serfaty; P. Girard
The impact of TDF on liver fibrosis dynamics has not been well characterized on the long term.
Co-infected patients from the French HIV-HBV Cohort were included in
the present analysis when treated with TDF. The level of fibrosis was estimated
using a biochemical score (Fibrometer«). Time-adjusted change in Fibrometer«
score from baseline (DAVG) was modeled at every 12-months after treatment
initiation using GEE models adjusted for serum HBV-
One hundred and forty-one co-infected patients were treated with tenofovir and followed for a median of 29.4 months (IQR 16.3). At baseline, 75 patients (mean age: 41.2 years, SD 7.3) presented with Fibrometer« stage F0-F1-F2 and 68 patients (mean age: 44.0 years, SD 7.8) with stage F3-F4. The majority of patients were treated with lamivudine at baseline (mean duration: 55 months, SD 19.6). Among patients with F3-F4 baseline fibrosis stages, there was a steep decline in fibrosis score at 12 months (adj DAVG=-0.127; 95% CI: -0.206, -0.047; p=0.002) proceeded by a slow and stable decline at 24 and 36 months of treatment (adj DAVG=-0.146; 95% CI: -0.245, -0.048; p=0.004 and adj DAVG=-0.167; 95% CI: -0.316, -0.018; p=0.03 respectively). A larger decline in Fibrometer« score was found in patients with F4 than F3 (adj DAVG at 36-months=-0.233 and -0.106, respectively). Patients with F0-F1-F2 baseline fibrosis remained consistently stable over follow-up (adj DAVG at 36-months=0.017; 95% CI: -0.102, 0.136; p=0.8). Among 38 pairs of biopsies, a 1 point-decrease in METAVIR stage was observed in 10 patients while 5 progressed and 23 remained stable.
TDF induced a significant decrease in fibrosis level after a mean treatment duration of 29.6 months. This is in favor of its extending use in HBV-infected patients.
922. De Novo Combination Therapy of Tenofovir Disoproxil Fumarate (TDF) Plus Lamividine (LAM) or TDF Plus Emtricitabine (FTC) Is Associated with Early Virologic Response in HIV/HBV Co-infected Patients
O. Lada; A. Gervais; M. Branger; G. Peytavin; G. Collin; G. Fraqueiro; R. Moucari; S. Males; M. Martinot-Peignoux; S. Matheron; P. Marcellin
Tenofovir disoproxil fumarate (TDF) has been recently approved for
treatment of chronic HBV. The aim of this retrospective study was to compare
the early virologic response of de novo combination therapy with TDF+LAM or
TDF+FTC with add-on therapy of LAM+TDF among HIV/HBV co-infected patients
followed from 2003-2006 at
Group I patients received de novo combination therapy of TDF+LAM or
TDF+FTC. These patients had either never received LAM or had not received LAM
in the last 4 years. Group II patients received add-on TDF+LAM (TDF added to
current LAM therapy). Early virologic response (ER) to TDF was defined as HBV-
We treated 141 HIV-HBV co-infected patients (131 LAM experienced) with
TDF in our center. At initiation of TDF, 57/141 subjects had VL under 3 log
IU/mL and 61 had VL >3 log UI/mL. Of these, 15/61 received de novo
combination therapy (Group I), and 46 received add-on combination (Group II).
All Group I patients (100%) achieved ER at M6 versus 75% in group II (p=0.035).
Fourteen Group II patients met criteria for
In our cohort of HIV/HBV co-infected patients de novo combination therapy appears to lead to an earlier virologic response than add-on therapy. De novo combination therapy should be considered in HIV/HBV co-infected patients. We observed a small subgroup of patients with delayed response to TDF. The reason is unclear and may possibly be related to the multiple LAM resistance mutations. No new mutations were identified among the delayed responders. Ongoing viral phenotyping analyses will further clarify this observation.
967. Prior Lamivudine (LAM) Failure May Delay
Time to Complete HBV-
P. Tuma; M. Bottecchia; J. Sheldon; J. Medrano; E. Vispo; A. Madejˇn; L. Martin-Carbonero; P. Barreiro; V. Soriano
Tenofovir (TDF) has recently
been approved in
Methods: Retrospective analysis of serum HBV-
A total of 56 HIV/HBsAg+
patients (mean age 45.1 years, 89% males) were identified. Their mean follow-up
was 826 patients-months. In 9 patients TDF+LAM was part of their first
antiretroviral regimen, while 47 had prior LAM experience. In this last group,
TDF was added even when serum HBV-
A total of 49 patients (88%)
showed undetectable serum HBV-
Dual therapy with TDF+LAM
provides serum HBV-
E. Formentini; A. U. Neumann; M. G. Ghany; A. C. Frank; R. T. Davey; S. Kottilil
Coinfection with HIV and hepatitis B virus (HBV) substantially alters the natural course of HBV infection as well as its management. Use of directly acting anti-HBV agents have been successful in suppressing HBV viral levels, but the kinetics of HBV viral decline and the factors that predict antiviral effect of nucleoside analogs have not yet been clearly established. In this study, we evaluated the HBV viral kinetics to adefovir therapy among lamivudine resistant HBV-infected HIV positive and negative patients
A double blind, randomized placebo-controlled study of HIV infected (N=12) and uninfected (N=5) chronic HBV patients treated with adefovir was conducted. All five HIV uninfected patients received adefovir, whereas co-infected patients were randomized to receive adefovir (n=8) or placebo (n=4) for a total of 48 weeks. At the end of 48 weeks, all patients received open label adefovir for an additional 48 weeks. HBV and HIV viral loads were performed on days 0, 1, 3, 5, 7, 10, 14, 28, and then every 4 weeks by Bayer bDNA 3.0 assay. Immune profile, liver chemistry and safety labs were performed at baseline and then serially after initiating treatment.
A significantly lower HBV viral decline was observed among co-infected patients receiving active drug when compared to that seen in monoinfected patients at week 4, (Median log -2.54 vs. -3.52, p<0.03) and at the end of treatment (Median log -5.37 vs. -7.00, p<0.03). Adefovir pharmacokinetics were similar in both groups (p>0.5). Baseline CD4+ T cell counts correlated positively with second slope decline of HBV in all patients (r=0.8; p<0.001), particularly in co-infected patients (r=0.65; p<0.05). Co-infected patients with CD4+ T cell counts less than 600 cells/mm3 had a much lower HBV viral load decline than those with CD4+T cell counts > 600 cells/mm3 (p <0.05).
HIV co-infection 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. The pharmacokinetics of adefovir was not affected by HIV serostatus and did not predict HBV viral response in both HIV negative and HIV positive subjects. Future studies will focus on evaluating the relationship between baseline CD4+ T cell counts and long-term suppression of HBV.
H. Castel; L. Bocket; C. Tamalet; M. BourliŔre; Y. Yazdanpanah
When approved by drug
regulatory authorities, entecavir (
assess the effect of
HIV-HBV co-infected pts
Four men with HBeAg-positive
Entecavir monotherapy has a
significant anti-HIV activity and can select for M184V mutation in a high
proportion of HIV-HBV pts, including those, as demonstrated here, who are
LAM-na´ve pts. Thus,
852. Inter- and Intra-genotypic
Recombinations of HBV
G. Fallot; T. Durand; A. Roque-Afonso; M. Gassin; E. Billaud; A. Gervais; S. Matheron; D. Samuel; C. Feray
HBV as well as HIV can be the object of genomic recombinations due to the jump of the reverse transcriptase between different genomes. Intergenotypic HBV recombinants are described in different populations but their emergence in an individual has never been described. The aim of this study was to longitudinally analyze the variability of the whole HBV genome in patients submitted to antiretroviral therapies.
Patients and Methods
Twenty-three HIV and HBV coinfected and
9 HBV monoinfected subjects were included. All plasma samples were obtained in
patient with marked HBV viremia (>log5) at least twice (mean interval= 51
months ▒ 24). They received 3TC,
RFLPľSSCP showed a marked variability of
This is the first demonstration of the occurrence of inter- as well intra-genotypic recombinations of HBV during the follow-up of chronically infected patients. These recombinant events deeply modified the HBV quasispecies. These phenomenon were frequent, at least among HIV coinfected subjects with high HBV viremia, and increased the possibility of immune and drug escape strains.