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Number of HIV-1 founder variants determined by source partner infection

July 02, 2020

For people infected by HIV in the subset of cases involving several variants of the virus, and for which disease progression is usually faster, a new modeling study suggests the number of infection-initiating viral variants is primarily determined by how long the source partner has been infected. According to the results of this work, which uniquely accounts for the sexual partner from whom the infection was acquired, the risk for multiple-founder variant transfer during sexual HIV exposure is nearly doubled during the first three months of the source partner's infection. These insights into the genetics of transmissible HIV strains could be crucial to developing effective HIV vaccine strategies. Despite the high genetic diversity of viruses in individuals with HIV-1, sexual transmission of the disease often only results from the passing of a single "founder" variant, which initiates the recipient's infection. But for some individuals - roughly 25% - infections involve several founding variants, which causes cases that exhibit faster disease progression and poorer clinical outcomes. While some evidence suggests that both viral and recipient partner factors may play a role in this genetic bottleneck, many studies evaluating multiple-founding HIV variants often lack data concerning the sexual partner from whom the infection was acquired. As a result, little is known about the importance of the source partner in determining the diversity of potential founder variants during sexual HIV exposure. Christian Julian Villabona-Arenas and colleagues analyzed sequence data on 112 sexual pairs in which the direction of transmission and infection stage of the source partner were known and used the data to create a phylodynamic model of founder-variant transmission. The results demonstrated that source partners with acute HIV-1 infections (those infected less than 90 days) are twice as likely to transmit multiple founder strains than those in the chronic stage of infection (infection older than 90 days), regardless of their sexual risk group (i.e., heterosexual or men-who-have-sex-with-men). The findings are contrary to claims arguing that some sexual risk groups are, in themselves, more physiologically prone to higher numbers of transmissible variants than others, illustrating the need for clinical analysis of known transmission pairs when evaluating the effect of sexual risk groups in HIV-1 infection.
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American Association for the Advancement of Science

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