FIG 4.

Time-of-addition studies in HBV-infected PHHs. Cryopreserved primary human hepatocytes (PHHs) were infected with HBV (derived from HepG2.2.15 cell culture supernatant). Compounds were added at 0, 4, 8, 24, or 48 h postinfection at the concentration ranges shown and replenished as indicated. Cells were treated until day 11 postinfection. Extracellular HBV DNA levels and intracellular HBV RNA levels were quantified by qPCR. The HBe/cAg and HBsAg levels in the cell culture supernatant were detected by AlphaLISA. The data represent mean values from at least 2 replicates. Error bars show standard deviations. CPD, compound; D, day; HBe/cAg, hepatitis B e antigen and hepatitis B core-related antigen; HBsAg, hepatitis B surface antigen; hpi, hours postinfection; TDF, tenofovir disoproxil.