Tenofovir (Viread), a nucleotide analog approved for HIV treatment, has also demonstrated antiviral activity in patients with chronic hepatitis B virus (HBV) infection.

The aim of the present study, presented at the 43rd annual meeting of the European Association for the Study of the Liver (EASL) last week in Milan, was to evaluate the rate of primary non-response to tenofovir in treatment-experienced HIV-HBV coinfected patients.

The analysis included 147 HIV-HBV coinfected individuals. Approximately 90% were had previously bee treated with lamivudine (Epivir-HBV; 3TC). Patients treated with tenofovir were evaluated for primary non-response, defined as HBV DNA decrease less than 1 log after 6 months of therapy.

The median treatment duration was 37 months (range 14-56). Serum HBV DNA levels and adherence to therapy were assessed at baseline and at 6 months of tenofovir therapy. The HCV polymerase region was sequenced and analysed for primary non-responders to look for resistance mutations.

Result

• Among 147 patients treated with tenofovir, 14 exhibited primary non-response. Measurement of tenofovir plasma concentrations clearly demonstrated non-adherence in 7 patients.

• Among the remaining 7 patients, 6 were men, the median age was 44 years, all were hepatitis B "e" antigen (HBeAg) positive, and the median baseline HBV DNA level was 6.42 log copies/mL (range 4.4-7.6).

• Patients had received lamivudine for a median of 34 months (range 12-117) before tenofovir was added.

• No patients had received adefovir (Hepsera).

• 4 patients were infected with HBV genotype G (2 coinfected with genotype A), 2 with genotype A, and 1 with genotype E.

• As expected among this group of heavily pre-treated patients, there was a high incidence of resistance-associated mutations at baseline, including rtV173l (28%), rtL180M (57%), rtA181T (14%), rtV191I (28%), S202I (14%), rtM204V (57%), rtL229M (28%).

• The rtA194T mutation was not observed, and no new mutations were detected at 6 months.

• All patients developed a subsequent response to tenofovir and achieved a low serum HBV DNA level after a median of 20 months (rage 17-24) of therapy.

Conclusion

"We identified a small subgroup of patients with delayed response to tenofovir," the researchers stated. "The reason is unclear and may be related to poor adherence, degree of HIV-related immunosuppression, or possibly, the multiple lamivudine resistance mutations in this heavily pre-treated population."

Service d'Hépatologie and INSERM CRB3, AP-HP Hôpital Beaujon, Clichy, France; Service des maladies infectieuses , AP-HP Hôpital Bichat Claude Bernard, Paris, France; Service de Virologie, AP-HP Hôpital Bichat Claude Bernard, Paris, France; Service de pharmacie clinique, AP-HP Hôpital Bichat Claude Bernard, Paris, France

5/02/08

Reference
O Lada, A Gervais, M Branger, and others. Low rate of delayed response in lamivudine experienced HIV/HBV co-infected patients treated with tenofovir disoproxil fumarate (TDF). 43rd Annual Meeting of the European Association for the Study of the Liver (EASL 2008). Milan, Italy. April 23-27, 2008. 43rd Annual Meeting of the European Association for the Study of the Liver (EASL 2008). Milan, Italy. April 23-27, 2008.