Periodic Reporting for period 4 - HIV ECLIPSE (HIV-1 acquisition and the future of prevention strategies: deciphering the eclipse phase through modelling and phylogenetics)
Periodo di rendicontazione: 2021-08-01 al 2023-01-31
The eclipse phase of HIV infection spans the time between an individual’s exposure to infection and them having detectable virus in their blood. The role of the eclipse phase in determining HIV establishment and the progression to AIDS remains unclear. In this project, we will test two hypotheses: First, that the HIV eclipse phase determines stochastic extinction events of potential founder strains after exposure and determines the success of HIV acquisition. Second, that eclipse phase dynamics can ultimately determine a patient's trajectory through later infection. To address these aims, we will use different quantitative approaches to understand the spread of HIV within an individual and the onward transmission to another person.
This work will likely lead to new insights about how HIV infection becomes established, why vaccine candidates have failed, and advance the use of quantitative methodology in this understudied but important area.
This work will likely lead to new insights about how HIV infection becomes established, why vaccine candidates have failed, and advance the use of quantitative methodology in this understudied but important area.
Work conducted during this period has principally been concerned with determining how transmitting partner factors affect the eclipse phase. Specifically, we have evaluated how the recency of infection in the transmitting partner (i.e. early or late infection) affects the probability of infection in the recipient partner and the number of founder variants transmitted.
Our work has found that the transmitting partner during sexual exposure determines both the number of virus particles and the number of founding variants that establishes infection in the recipient partner. That is, during early infection, the transmitting partner is responsible for transmitting twice the number of founding variants as would be transmitted during the later stage of infection.
Our work has found that the transmitting partner during sexual exposure determines both the number of virus particles and the number of founding variants that establishes infection in the recipient partner. That is, during early infection, the transmitting partner is responsible for transmitting twice the number of founding variants as would be transmitted during the later stage of infection.
To achieve our goals, we have developed new methods to combined phylogenetic results with mathematical modelling to understand the transmission of virus between individuals. We have also developed statistical matching methods to extend phylogenetic analysis to understand unobserved processes such as the number and type of viruses that are transmitted during exposure.