Reconciling founder variant multiplicity of HIV-1 infection with the rate of CD4+ decline
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+ 4 T cell decline may be elevated, but these findings remain inconsi...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Royal Society
2024
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| _version_ | 1811141142237937664 |
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| author | Baxter, J Villabona-Arenas, J Thompson, RN Hue, S Regoes, R Kouyos, R Gunthard, H Albert, J Brown, AL Atkins, K |
| author_facet | Baxter, J Villabona-Arenas, J Thompson, RN Hue, S Regoes, R Kouyos, R Gunthard, H Albert, J Brown, AL Atkins, K |
| author_sort | Baxter, J |
| collection | OXFORD |
| description | 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+ 4 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 associating with higher SpVL. Next, we combined models of HIV-1 transmission, heritability and disease progression to understand whether available data suggest a faster CD4+ T cell decline would be expected to associate with multiple variant infection, without an explicit dependency between the two. 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+ 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+ T cell decline, further investigation is required to establish a causal basis for this association. |
| first_indexed | 2024-09-25T04:33:10Z |
| format | Journal article |
| id | oxford-uuid:3e01dc01-a994-4efb-bd8f-3b2312a3fc7a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:33:10Z |
| publishDate | 2024 |
| publisher | Royal Society |
| record_format | dspace |
| spelling | oxford-uuid:3e01dc01-a994-4efb-bd8f-3b2312a3fc7a2024-09-10T08:51:01ZReconciling founder variant multiplicity of HIV-1 infection with the rate of CD4+ declineJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3e01dc01-a994-4efb-bd8f-3b2312a3fc7aEnglishSymplectic ElementsRoyal Society2024Baxter, JVillabona-Arenas, JThompson, RNHue, SRegoes, RKouyos, RGunthard, HAlbert, JBrown, ALAtkins, KHIV-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+ 4 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 associating with higher SpVL. Next, we combined models of HIV-1 transmission, heritability and disease progression to understand whether available data suggest a faster CD4+ T cell decline would be expected to associate with multiple variant infection, without an explicit dependency between the two. 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+ 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+ T cell decline, further investigation is required to establish a causal basis for this association. |
| spellingShingle | Baxter, J Villabona-Arenas, J Thompson, RN Hue, S Regoes, R Kouyos, R Gunthard, H Albert, J Brown, AL Atkins, K Reconciling founder variant multiplicity of HIV-1 infection with the rate of CD4+ decline |
| title | Reconciling founder variant multiplicity of HIV-1 infection with the rate of CD4+ decline |
| title_full | Reconciling founder variant multiplicity of HIV-1 infection with the rate of CD4+ decline |
| title_fullStr | Reconciling founder variant multiplicity of HIV-1 infection with the rate of CD4+ decline |
| title_full_unstemmed | Reconciling founder variant multiplicity of HIV-1 infection with the rate of CD4+ decline |
| title_short | Reconciling founder variant multiplicity of HIV-1 infection with the rate of CD4+ decline |
| title_sort | reconciling founder variant multiplicity of hiv 1 infection with the rate of cd4 decline |
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