The tipping point ratio (i.e. theoretical TPR), defined as the yearly ratio of new HIV infections to the net increase in HIV+ individuals on antiretroviral therapy (ART), has been used to compare ART scale-up efforts across countries and measure their progress toward HIV elimination. However, in the literature, estimates of TPR are often based on a definition, using new ART initiations as the denominator (i.e. practical TPR), which is easier to estimate. We analyze the utility of TPR, theoretical and practical, to evaluate the progress of ART rollout using different definitions under various epidemic conditions.
We developed a compartmental model of HIV transmission and ART rollout in South Africa, calibrated to 2012 epidemic data and reflecting expansion to universal treatment in 2017. We used Monte Carlo filtering to select 1000 simulations which represented uncertainty in base-case epidemic conditions. We simulated scenarios in which the theoretical TPR is targeting a fixed value between 0.6 and 1.8 over 2020-2024 using compensation for losses of individuals on ART over time (due to deaths and interrupted ART) and different ART access strategies by stage of HIV progression (late or early ART initiation). We compared the reduction in HIV incidence relative to the base-case epidemic in 2024 as function of the practical or theoretical TPR (averaged over 2020-2024) and ART coverage in 2024.
Results show that the same HIV incidence reduction (35%) can be achieved with a wide range of TPR (theoretical TPRs 0.68-1.58; practical TPRs 0.42-0.72). Practical TPR which counts ART compensation as new initiations yields lower incidence reduction for the same value as theoretical TPR, e.g. TPR = 0.8 has 19-30% incidence reduction under practical definition and 29-54% under theoretical definition (Fig A). Simulated ART coverage achieved in 2024 (Fig B) is a better predictor of HIV incidence reduction (with Pearson’s r = 0.85) than theoretical TPR (Pearson’s r = -0.79). The difference between early and late ART initiation is small due to ART compensation.
Our analysis suggests some confusion when TPR is used in the literature. The practical TPR likely overestimates the progress of ART programs and often produces TPR values below 1. Although a more reasonable indicator, the theoretical TPR is technically more difficult to estimate and should be supplemented with ART coverage data to judge the progress of ART programs.