Understanding HIV reactivation and latency

Research program: 
Currently recruiting: 
The challenge: 

Antiretroviral therapy is able to suppress HIV replication in most infected individuals. However, treatment must be continued for life in most cases, as the virus rapidly regrows from a ‘latent reservoir’ if treatment is stopped. A number of drugs are being developed to “purge” the latent reservoir, to prevent or delay the regrowth of virus when treatment is stopped. However, measuring the levels of this latent virus is challenging, and modelling can help us understand this.

The project: 

Using a mathematical modelling approach, we are developing new analytical methods to measure how often HIV reactivates from latency, to estimate how effective current treatments are, and how effective they would need to be to give remission from HIV. We collaborate with a number of experimentalists and clinicians both in Australia and around the world who provide data from animal studies and clinical trials.

The method: 

We use a combination of mathematical modelling and viral sequence analysis to estimate the rate of HIV reactivation from latency, and are exploring new ways to study this.

The results: 

We have provided the first direct estimate of how often HIV successfully ‘wakes up’ from latency after treatment interruption – and find this is only around once a week. We are now developing new modelling approaches to understand how best to measure this reactivation rate in clinical trials, in order to test the effectiveness of new ‘anti-latency’ drugs.

The impact: 

The techniques we are developing will be essential for discovery and optimisation of the use of new ‘anti-latency’ interventions.

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