Patterns of circulating hepatitis B virus serum nucleic acids during lamivudine therapy

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Abstract
We examined whether lamivudine treatment, in addition to the rapid decline of HBV serum DNA described in a large number of laboratories, causes changes in composition and amount of discernable circulating viral DNA and RNA. Nucleic acids were extracted from serial serum samples of a patient infected chronically and treated with lamivudine for 14 weeks. Three sequence segments of the HBV genome synthesized successively during replication, X, C, and X‐preC, were analyzed by competitive PCR and RT/PCR. In addition, RNA was examined for differential polyadenylation. Before treatment, identical DNA copy numbers (109/ml) were found in all three segments. C segment DNA displayed the expected rapid decline. X‐preC, a target contiguous only on plus‐strand DNA behaved similarly. In contrast, the X segment DNA copy numbers showed a less pronounced decrease remaining at higher values (107/ml) than the C and X‐preC segment (both about 2 × 105/ml) at the end of therapy. X segment RNA displayed a persisting copy number of about 107/ml, while C and X‐preC RNA decreased to about 105 copies/ml. Polyadenylated HBV RNA, full‐length and truncated, persisted initially at 105 but decreased to 104 to 103 copies/ml at the end of treatment. The major conclusions are the actual numbers of virus particles during lamivudine therapy can only be assessed via X segment DNA, since it is reverse transcribed first, and Lamivudine induced coexistence of DNA and RNA for the C and X segment at similar levels indicates drug‐arrested intermediates of reverse transcribed HBV DNA minus‐strand. Packaged RNA lacks a poly(A) tail whereas polyadenylated RNA is likely not packaged. J. Med. Virol. 71:24–30, 2003.