Christoph Stephan*1, Amina Carlebach1, Thomas Lutz1, Annemarie Berger2, Brenda Dauer1,
Markus Bickel1, Stephan Klauke1, Martin Stuermer2, and Schlomo Staszewski1

1 HIV Research and Treatment Unit, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany; 2 Medical Virology Institute, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany    

Background:
We studied the impact of tenofovir disoproxil fumarate, given as an antiretroviral medication, on patients with chronic hepatitis B-virus co-infection.

Methods:
The polymerase gene-sequence evolution and quantitative hepatitis B virus loads (HBVL) were observed for 48 weeks in patients taking tenofovir-containing antiretroviral therapy. The patients were grouped according to baseline strata: Highly-replicative virus (> 6 log copies/mL), low-replicative virus at detectable virus loads (< 6 log) and HBs-antigen positive, hepatitis B virus-DNA negative individuals.

Results:
31 patients were evaluated. The median HBVL decline in 20 pts with high-replicative virus was -5.37 log (range: 3.57–7); 11/20 decreased to undetectable levels (lower limit of detection = < 200 copies/mL) and another three were below 400 copies/mL. The virologic response of the high-replicative virus group is shown in the figure, in relation to YMDD-positive (grey) or -negative mutation status. Out of six patients with detectable hepatitis B virus-DNA at week 48 (HBVL range: 3.36–4.32 log10), we were able to perform a re-sequence in four patients. We did not observe relevant emerging resistance mutations, nor a virus load re-increase from nadir > + 0.5 log. Suboptimal responders are shown by circles (YMDD-negative) and boxes (YMDD-positive). The patients with low-replicative virus (n= 9) and the baseline DNA-negative patients (n= 2) had an undetectable hepatitis B virus-DNA at week 48. Two patients became HBeAg-negative; one DNA negative patient became HBsAg-negative.

Conclusions:
Tenofovir is effective in treating hepatitis B virus infection in HIV-patients. Patients with high-replicative virus may benefit from this treatment strategy by a reduction in replicative status, a condition necessary for improved hepatic function. A few patients showed low-level HBV replication. Clinical resistance of hepatitis B virus to tenofovir was not observed during the 48 weeks.


Figure:
Virus Load determination over time in 20 patients with high-replicative virus, depending on YMDD-mutation status (grey lines/circles: YMDD positive).