{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:47:08Z","timestamp":1787010428742,"version":"build-2736575974"},"reference-count":60,"publisher":"The Royal Society","issue":"219","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["J. R. Soc. Interface."],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:p>\n                    HIV-1 transmission precipitates a stringent genetic bottleneck, with 75% of new infections initiated by a single genetic variant. Where multiple variants initiate infection, recipient set point viral load (SpVL) and the rate of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell decline may be elevated, but these findings remain inconsistent. Here, we summarised the evidence for this phenomenon, then tested whether previous studies possessed sufficient statistical power to reliably identify a true effect of multiple variant infection leading to higher SpVL. Next, we combined models of HIV-1 transmission, heritability and disease progression to understand whether available data suggest a faster CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell decline would be expected to associated with multiple variant infection, without an explicit dependency between the two. First, we found that most studies had insufficient power to identify a true significant difference, prompting an explanation for previous inconsistencies. Next, our model framework revealed we would not expect to observe a positive association between multiple variant infections and faster CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell decline, in the absence of an explicit dependency. Consequently, while empirical evidence may be consistent with a positive association between multiple variant infection and faster CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell decline, further investigation is required to establish a causal basis.\n                  <\/jats:p>","DOI":"10.1098\/rsif.2024.0255","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T20:06:06Z","timestamp":1730232366000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Reconciling founder variant multiplicity of HIV-1 infection with the rate of CD4\n                    <sup>+<\/sup>\n                    decline"],"prefix":"10.1098","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6598-1784","authenticated-orcid":true,"given":"James","family":"Baxter","sequence":"first","affiliation":[{"name":"Usher Institute, Edinburgh Medical School, The University of Edinburgh , Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9928-3968","authenticated-orcid":true,"given":"Ch. Juli\u00e1n","family":"Villabona-Arenas","sequence":"additional","affiliation":[{"name":"Faculty of Epidemiology and Population Health, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine , London, UK"},{"name":"Centre for Mathematical Modelling of Infectious Diseases, London School of Hygiene and Tropical Medicine , London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8545-5212","authenticated-orcid":true,"given":"Robin N.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Mathematical Institute, University of Oxford , Oxford OX2 6GG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8580-6905","authenticated-orcid":true,"given":"St\u00e9phane","family":"Hu\u00e9","sequence":"additional","affiliation":[{"name":"Faculty of Epidemiology and Population Health, Department of Infectious Disease Epidemiology, London School of 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Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1142-6723","authenticated-orcid":true,"given":"Huldrych F.","family":"G\u00fcnthard","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich , Zurich, Switzerland"},{"name":"Institute of Medical Virology, University of Zurich , Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9020-0521","authenticated-orcid":true,"given":"Jan","family":"Albert","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institute , Stockholm, Sweden"},{"name":"Department of Clinical Microbiology, Karolinska University Hospital , Stockholm, 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