Modelling of anti-latency treatment in HIV; What is the optimal duration of anti-retroviral-free HIV remission?

3 years ago

Modelling of anti-latency treatment in HIV; What is the optimal duration of anti-retroviral-free HIV remission?

Pinkevych, Lewin, Davenport, Rasmussen, Kent, Cromer

A number of treatment strategies are currently being developed to promote anti-retroviral free HIV cure or remission. While complete elimination of the HIV reservoir would prevent recurrence of infection, it is not clear how different remission lengths would affect viral rebound and transmission. In this work we use a stochastic model to show that a treatment that achieves a one-year average time to viral remission will still lead to nearly a quarter of subjects experiencing viral rebound within the first three months. Given quarterly viral testing intervals, this leads to an expected 39 (95%UI 22-69) heterosexual transmissions and up to 262 (95%UI 107-534) homosexual transmissions per 1,000 treated subjects over a 10-year period. Thus, a balance between high initial treatment levels, risk of recrudescence, and risk of transmission should be considered when assessing the 'useful' or optimal length of anti-retroviral-free HIV remission to be targeted. We also investigate the trade-off between increasing the average duration of remission, versus the risk of treatment failure (viral recrudescence) and the need for re-treatment. To minimise drug exposure, we find that the optimal target of anti-latency interventions is a 1700-fold reduction in the size of the reservoir, which would lead to an average time to recrudescence of 30 years. Interestingly, this is a significantly lower level of reduction than that required for complete elimination of the viral reservoir. Additionally we show that when shorter periods are targeted, there is a real probability of viral transmission occurring in between testing for viral rebound.Importance Current treatment of HIV involves patients taking anti-retroviral therapy to ensure that the level of virus remains at very low, or undetectable levels. Continuous therapy is required, as the virus persists in a latent state within cells, and when therapy is stopped the virus rebounds, usually within a couple of weeks. A major question is how to reduce the amount of persistent virus, and therefore allow a delay or remission until the virus returns after ceasing therapy. In this work we consider the probability that HIV will still rebound even after this reduction, and ask what the likelihood of viral transmission would be in this case.

Publisher URL: http://doi.org/10.1128/JVI.01395-17

DOI: 10.1128/JVI.01395-17