Reconciling founder variant multiplicity of HIV-1 infection with the rate of CD4$^{+}$ decline
Year: 2024
Type: article
Abstract: 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$^{+}$ 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 $^{+}$ 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 $^{+}$ 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.
DOI: 10.5167/uzh-264443
Authors: Baxter, James, Villabona-Arenas, Ch Julián, Thompson, Robin N, Hué, Stéphane, Regoes, Roland R, Kouyos, Roger D, Günthard, Huldrych F, Albert, Jan, Leigh Brown, Andrew, Atkins, Katherine E
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W6892256137
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