Analysis of hepatitis B virus genotype changes in patients with chronic hepatitis B infection on tenofovir therapy

Antiviral therapy for chronic hepatitis B (CHB) is often required for prolonged periods. We investigated the instance of one HBV genotype switching to another during tenofovir therapy. Of the 67 patients, genotype A was present in 6 (8.9%), D in 43 (65.6%), C in 1 (1.5%), and mixed in 17 (23.8%) patients. Genotype changes were detected in 51 (76.1%) patients on therapy during a follow‐up of 192 (range 52–312) weeks. Inter‐genotype changes were seen in 17 (33.3%) and intra‐genotype in 28 (55%) and both inter‐ and intra‐genotype in 6 of 51 (11.7%) patients. The distribution of genotypes in patients achieving complete virological response was genotype D, 32/43 (74.4%); genotype A, 6/6 (100%); and mixed genotypes, 13/17 (76.47%). The cumulative time of genotype switch among genotype A was 12 months (range 6–18), in genotype D, 12 months (range 6–48), and mixed genotype, 18 months (range 6–24). The type of inter‐genotype switch most frequently detected among genotype A1 was from A1 to D1 5/6 (83.3%), followed by mixed to genotype D3 7/13 (54%) and among intra‐genotype changes, from D1 to D3 in 14/20 (70%). Pretreatment HBV genotype was the only factor predicting inter‐genotype switches with genotype A or mixed genotypes more likely to undergo inter‐genotype switches as compared to genotype D patients (OR 66.6 [13.6–327.0, P < 0.001]). Compared to genotype D, genotype A, and mixed genotypes are more inclined to switch while on tenofovir therapy. Genotypes tend to switch and select to a particular type possibly due to constant antiviral drug pressure. J. Med. Virol. 88:1364–1375, 2016. © 2016 Wiley Periodicals, Inc.