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GS\u2010US\u2010174\u20130115 was a double\u2010blind, placebo\u2010controlled, Phase 3, 192\u2010week clinical trial that evaluated TDF in adolescents with chronic hepatitis B (CHB). HBV full\u2010genome deep sequencing was performed using Illumina MiSeq at baseline (BL; <jats:italic>n<\/jats:italic>\u00a0=\u00a085), Week 8 (W8; <jats:italic>n<\/jats:italic>\u00a0=\u00a080), Week 72 (W72; PBO only, <jats:italic>n<\/jats:italic>\u00a0=\u00a042), and treatment\u2010free follow\u2010up (TDF only, <jats:italic>n<\/jats:italic>\u00a0=\u00a025). The viral diversity was calculated using Shannon entropy and population nucleotide diversity with a 2% variant cutoff. Our data showed (i) a higher viral diversity in the X region at baseline than the core\/polymerase\/surface regions, (ii) higher core\/surface viral diversity at baseline for patients with seroconversion, (iii) an expected reduction in viral diversity after 8\u00a0weeks of TDF treatment, and (iv) a drop in viral diversity at W72 for patients receiving placebo with a seroconversion (<jats:italic>n<\/jats:italic>\u00a0=\u00a07). The higher viral diversity in X was associated with higher baseline alanine aminotransferase (ALT) levels (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001). Patients with greater reduction of diversity at W8 of TDF treatment had higher baseline ALT levels. For placebo patients who seroconverted, the drop in viral diversity at W72 (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.04) coincided with reduction of serum HBV DNA (average change from baseline\u00a0=\u00a0\u22124.10\u00a0log10 copies\/ml) and unique combinations of variants were enriched in a patient's viral population post seroconversion. The basal core promoter (BCP) variants, A1762T and G1764A, and the pC variant, G1896A, were most often enriched at or after seroconversion.<\/jats:p>","DOI":"10.1111\/jvh.13547","type":"journal-article","created":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T09:11:00Z","timestamp":1621329060000},"page":"1160-1168","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hepatitis B virus genome diversity in adolescents: Tenofovir disoproxil fumarate treatment effect and HBeAg serocon version"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7348-3520","authenticated-orcid":false,"given":"Christophe","family":"Combet","sequence":"first","affiliation":[{"name":"Centre L\u00e9on B\u00e9rard Centre de Recherche en Canc\u00e9rologie de Lyon (CRCL) Universit\u00e9 de Lyon Universit\u00e9 Claude Bernard Lyon 1 INSERM 1052 CNRS 5286  Lyon Cedex France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neeru","family":"Bhardwaj","sequence":"additional","affiliation":[{"name":"Foundation Medicine  Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Hedskog","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc.  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