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Consensus sequences were made from paired-end Illumina reads with a target-capture approach to amplify HIV material following poor success with standard approaches. In comparisons with a smaller \u2018intermediate\u2019 genome dataset from 1998 to 1999 and a \u2018modern\u2019 genome dataset from 2007 to 2016, the proportion of subtype D was significantly higher initially, dropping from 67% (73\/109), to 57% (26\/46) to 17% (82\/465) respectively (p\u2009&lt;\u20090.0001). Subtype D has previously been shown to have a faster rate of disease progression than other subtypes in East African population studies, and to have a higher propensity to use the CXCR4 co-receptor (\u201cX4 tropism\u201d); associated with a decrease in time to AIDS. Here we find significant differences in predicted tropism between A1 and D subtypes in all three sample periods considered, which is particularly striking the 1986 sample: 66% (53\/80) of subtype D <jats:italic>env<\/jats:italic> sequences were predicted to be X4 tropic compared with none of the 24 subtype A1. We also analysed the frequency of subtype in the envelope region of inter-subtype recombinants, and found that subtype A1 is over-represented in <jats:italic>env<\/jats:italic>, suggesting recombination and selection have acted to remove subtype D <jats:italic>env<\/jats:italic> from circulation. The reduction of subtype D frequency over three decades therefore appears to be a result of selective pressure against X4 tropism and its higher virulence. Lastly, we find a subtype D specific codon deletion at position 24 of the V3 loop, which may explain the higher propensity for subtype D to utilise X4 tropism.<\/jats:p>","DOI":"10.1186\/s12977-022-00612-5","type":"journal-article","created":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T05:03:46Z","timestamp":1670907826000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A large population sample of African HIV genomes from the 1980s reveals a reduction in subtype D over time associated with propensity for CXCR4 tropism"],"prefix":"10.1186","volume":"19","author":[{"given":"Heather E.","family":"Grant","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunando","family":"Roy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Tutill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget","family":"Ferns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia A.","family":"Cane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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