By Liz Highleyman

Hepatitis B Virus

Hepatitis B virus (HBV) easily develops mutations as it replicates, which can lead to rapid emergence of resistance to anti-HBV drugs, especially when used as monotherapy. Viral variants carrying point mutations in the reverse transcriptase (rt) domain have been detected in patients treated with lamivudine (Epivir-HBV) and adefovir (Hepsera).

In a study presented as a poster at the 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008), taking place this week in Washington, DC, Spanish researchers aimed to identify mutations associated with resistance to these drugs in 17 patients with chronic hepatitis B. Risk factors for HBV acquisition were sexual contact (21.4%), blood transfusion (14.3%), mother-to-child (7.1%), interfamilial (7.1%), or unknown (49.9%).

The investigators analyzed serum samples using the INNO-LIPA HBV DR v2 assay and the INNO-LIPA HBV genotyping assay. Nucleic acid was isolated and quantified using the COBAS Taqman real time HBV PCR assay. Levels of hepatitis B surface antigen (HBsAg), hepatitis B "e" antigen (HBeAg), and anti-HBs and anti-HBe antibodies were also measured.

Results

• HBV genotype D was the most prevalent form (58.8%), followed by genotype A (35.3%).

• 1 patient had confirmed dual infection with D/E genotypes.

• 3 of 12 patients (25%) treated with adefovir had detectable resistance mutations:

• 1 had dual mutations (rtA181V + rtN236T) after 21 months of treatment (HCV RNA 4.3 log10 copies/mL); this patient was HBeAg positive.

• 1 had a single mutation (rtA181V) after 3 years of treatment (HCV RNA 1.5 log10 copies/mL).

• 1 had a single mutation (rtN236T) after only 4 months of treatment (HCV RNA 4.8 log10 copies/mL).

• 2 of 4 patients (50%) treated with lamivudine had resistance mutations:

• 1 had dual mutations (rtL180M + rtM204I) after 9 months of treatment (HCV RNA 4.1 log10 copies/mL).

• 1 had a single mutation (rtM204I) after 18 months of treatment (HCV RNA 2.6 log10 copies/mL).

• All patients with resistance mutations were infected with HBV genotype D.

"INNO-LIPA is a convenient tool for detection HBV rt variability and genotype," the investigators concluded.

Resistance mutations "are associated with rapid virological breakthrough," they added, with 1 patient on adefovir developing a detectable mutation after just 4 months of treatment.

Univ. Basque Country, Bilbao, Spain; Basurto Hosp., Bilbao, Spain.

10/28/08

Reference
M Basaras, E Arrese, S Blanco, and others. Hepatitis B Virus Reverse Transcriptase Variability in Treated Chronic Patients. 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008). Washington, DC. October 25-28, 2008. Abstract V-1625.