HIV Reactivation from Latency after Treatment Interruption Occurs on Average Every 5-8 Days—Implications for HIV Remission
Fig 5
Modelling of kinetics of time-to-detection:
A: Using the ratio of the number of copies of reactivation founder viruses to estimate rate of initiation of viral growth. The cumulative proportion of founders with different ratios (to the size of next largest founder) is shown. Solid line is ratios from the experimental data, dashed line is the theoretical distribution with the best fit frequency of rebound of once every 3.6 (CI 1.98–6.62) days. Ratios marked with an asterisk are where we could only estimate a minimum ratio (ie: there was no detected next founder virus). (B) Estimating the reduction in frequency of recrudescence (and reservoir size) from observed delay to detection of virus. For a ‘normal’ reservoir size, we find an average frequency of reactivation of once every 6 days (which also equates to an average delay to reactivation of 6 days). For patients with longer time-to-detection we can estimate the relative size of the reservoir compared to our cohort populations. Solid line shows the fold reduction in reservoir size that would be estimated simply comparing the observed time to detection with the estimated average of 6 days. Since reactivation does not always occur at the average time, the range expected for 95% of subjects is shown (shaded area). T1 and T2 are the delays for two patients that underwent allogeneic stem cell transplantation (reference [30]). T3 is the delay observed in the ‘Mississippi baby’ (reference [29]). (C) Difficulties using treatment interruption studies to measure changes in the reservoir. The number of patients required (y-axis) to have a 50% (dashed line), an 80% (solid line) or a 95% (dot-dash line) power to detect a given reduction in reservoir (x-axis) is shown, based on Log-rank test. This assumes a 100-day follow up after ART-interruption.