Improving ART programme retention and viral suppression are key to maximising impact of treatment as prevention - a modelling study

Abstract

Background: UNAIDS calls for fewer than 500,000 new HIV infections/year by 2020, with treatment-as-prevention being a key part of their strategy for achieving the target. A better understanding of the contribution to transmission of people at different stages of the care pathway can help focus intervention services at populations where they may have the greatest effect. We investigate this using Uganda as a case study.

Methods: An individual-based HIV/ART model was fitted using history matching. 100 model fits were generated to account for uncertainties in sexual behaviour, HIV epidemiology, and ART coverage up to 2015 in Uganda. A number of different ART scale-up intervention scenarios were simulated between 2016 and 2030. The incidence and proportion of transmission over time from people with primary infection, post-primary ART-naïve infection, and people currently or previously on ART was calculated.

Results: In all scenarios, the proportion of transmission by ART-naïve people decreases, from 70% (61%-79%) in 2015 to between 23% (15%-40%) and 47% (35%-61%) in 2030. The proportion of transmission by people on ART increases from 7.8% (3.5%-13%) to between 14% (7.0%-24%) and 38% (21%-55%). The proportion of transmission by ART dropouts increases from 22% (15%-33%) to between 31% (23%-43%) and 56% (43%-70%).

Conclusions: People who are currently or previously on ART are likely to play an increasingly large role in transmission as ART coverage increases in Uganda. Improving retention on ART, and ensuring that people on ART remain virally suppressed, will be key in reducing HIV incidence in Uganda.

Keywords: ART; HIV; Retention; Sub-Saharan Africa; Transmission; Uganda.

Fig. 1

Model baseline fit to empirical data. Graphs a-f: Black dots show the empirical estimates, and the error bars show the acceptable ranges for the outputs used in fitting the model. Black lines show the median model output. Blue/green bands show 10% quantiles of model outputs. The full width of the band shows the range of the model output. Graphs g-i: Orange boxes show the empirical data and acceptable ranges. Green boxes show the model output. Model fits to the remaining 28 outcomes are shown in McCreesh et al. [10]

Fig. 2

Input parameter initial plausible ranges and fitted values. Histograms show the distribution of values in the 100 model fits for the seven transmission input parameters (a) baseline transmission; b) transmission probability from men to women, relative to transmission probability from women to men; c) relative transmission probability on established ART; d) relative transmission probability with CD4 count <200 cells/μl; e) relative transmission probability with CD4 count >350 cells/μl; f) relative transmission probability during primary infection; g) duration of primary infection (months)). Scatter graphs show the joint distribution of pairs of input parameters. The red lines show the initial plausible ranges, before model fitting. All plausible input ranges were independent of the values of other input parameters, with the exception of ‘primary transmission’ and ‘primary duration’ which had a two-dimensional joint plausible range. The plausible upper limit for ‘baseline’ was 1, and is not shown on the graphs

Fig. 3

a) Overall HIV prevalence in 2015 and 2030 by intervention; b) Proportion of HIV+ people by stage; c) Overall HIV incidence in 2015 and 2030 by intervention; d) HIV incidence by stage in 2015 and by stage and intervention in 2030; e) Proportion of new infections due to transmission by people in each stage in 2015 and by stage and intervention in 2030. Boxes show the median and 25–75% quartiles. Whiskers show the highest/lowest value that is within 1.5 times the inter-quartile range from the 75%/25% quartile. Crosses show the 90% plausible range. Results for 2015 are shown in black

Fig. 4

Incidence and proportion of HIV infection due to transmission by HIV+ people in each stage stage (first four rows), and overall HIV prevalence and incidence (bottom row), for the baseline, universal test and treat (UTT), and universal test, treat, and keep (UTTK) interventions. Lines show median, bands show 90% plausible range. Note different axis scales for overall