1. Boston University Slideshow Title Goes Here Eliminating CD4 thresholds in South Africa will not lead to large increases in persons receiving ART without further investment in testing, linkage, and initiation Jacob Bor, Shahira Ahmed, Matthew P. Fox, Sydney Rosen, Gesine Meyer-Rath, Ingrid Katz, Frank Tanser, Deenan Pillay, Till Bärnighausen No financial disclosures

2. Boston University Slideshow Title Goes Here Treatment for all?  WHO now recommends ART at HIV diagnosis, regardless of CD4 count  South Africa has announced that it will eliminate CD4 thresholds in September 2016

3. Boston University Slideshow Title Goes Here High expectations for “treat all” Expanding eligibility will increase numbers on ART  Reduce HIV morbidity and mortality  Lower population viral load, reduce HIV transmission  Potential to end epidemic HIV

4. Boston University Slideshow Title Goes Here High expectations for “treat all” Expanding eligibility will increase numbers on ART High ART uptake needed to meet targets  In South Africa, 6.5M HIV-infected, 3.4M on ART  90-90-90 implies 5.3M on ART  1.9M new patients, >50% increase in patients on ART

5. Boston University Slideshow Title Goes Here High expectations for “treat all” Expanding eligibility will increase numbers on ART High ART uptake needed to meet targets  In South Africa, 6.5M HIV-infected, 3.4M on ART  90-90-90 implies 5.3M on ART  1.9M new patients, >50% increase in patients on ART  Will eliminating CD4 thresholds help South Africa reach this goal?

6. Boston University Slideshow Title Goes Here  Empirically-based modeling study Using data on ART uptake among patients who had an eligible vs. not eligible CD4 count under previous guidelines (CD4<350), we project: (1)proportion of patients that will gain eligibility (CD4>500) (2)proportion of newly eligible patients (CD4>500) that would have initiated ART even under old guidelines (3)proportion of newly eligible patients (CD4>500) that are expected to initiate ART under new guidelines (4)effect of new guidelines on ART uptake among the eligible (3) – (2) (5)relative increase in numbers starting ART (6)number of new initiators in South Africa nationally (7)increase in programme costs How many new ART initiators can South Africa expect when CD4 thresholds are eliminated?

7. Boston University Slideshow Title Goes Here  Empirically-based modeling study  Data sources  All patients (n = 19,279) presenting in the Hlabisa HIV Treatment and Care Programme with a first CD4 count August 2011 - December 2013.  National estimates of patients receiving ART (NDOH)  National ART Cost Model (Meyer-Rath) How many new ART initiators can South Africa expect when CD4 thresholds are eliminated?

8. Boston University Slideshow Title Goes Here How many new ART initiators can South Africa expect when CD4 thresholds are eliminated? Distribution of first CD4 counts

9. Boston University Slideshow Title Goes Here How many new ART initiators can South Africa expect when CD4 thresholds are eliminated? Distribution of first CD4 counts Probability starts ART under new regime Probability starts ART under old regime

10. Boston University Slideshow Title Goes Here How many new ART initiators can South Africa expect when CD4 thresholds are eliminated? Distribution of first CD4 counts Probability starts ART under new regime Probability starts ART under old regime Difference is the causal effect of having an ART-eligible CD4 count on ART uptake. May vary CD4 count.

11. Boston University Slideshow Title Goes Here Source: Hlabisa HIV Treatment and Care Programme

12. Boston University Slideshow Title Goes Here Source: Hlabisa HIV Treatment and Care Programme 3 out of 5 patients seeking care already eligible

13. Boston University Slideshow Title Goes Here 8% of newly-eligible patients would initiate even under existing guidelines 8% Source: Hlabisa HIV Treatment and Care Programme

14. Boston University Slideshow Title Goes Here Significant increase in ART uptake with CD4-eligibility 25 percentage points Source: Hlabisa HIV Treatment and Care Programme

15. Boston University Slideshow Title Goes Here Lower ART uptake at higher CD4 counts P<0.001 Source: Hlabisa HIV Treatment and Care Programme

16. Boston University Slideshow Title Goes Here Lower ART uptake at higher CD4 counts Source: Chiu et al. (poster at AIDS 2016), Africa Centre for Population Health Proportion starting ART in 6 months

17. Boston University Slideshow Title Goes Here Starts ART under new regime Starts ART under old regime Source: Hlabisa HIV Treatment and Care Programme

18. Boston University Slideshow Title Goes Here 350-cell threshold 500-cell threshold No CD4 threshold

19. Boston University Slideshow Title Goes Here Source: Hlabisa HIV Treatment and Care Programme 72.8% 8.0% 19.2% Impact of eliminating CD4 thresholds

20. Boston University Slideshow Title Goes Here Upper bound (sensitivity analysis) 59.2% Impact of eliminating CD4 thresholds

21. Boston University Slideshow Title Goes Here Results Among Hlabisa patients presenting with CD4 ≥500 cells/μL…  8.0% initiated under the old regime.  19.2% are expected to start due to the policy change.  72.8% are expected not to start despite being eligible.  26.7% increase in ART initiators per year  Sensitivity analysis: 59.2% are expected not to start despite being eligible. Excludes any other changes in testing, linkage or initiation procedures.

22. Boston University Slideshow Title Goes Here Results National Projections…  164,000 (116,000 to 180,000) new initiators per year  5.2% increase in population on ART  5.0% increase in costs  Sensitivity analysis: 9.3% increase in population on ART Excludes any other changes in testing, linkage or initiation procedures.

23. Boston University Slideshow Title Goes Here Limitations  Future projections subject to uncertainty  One sub-district in rural South Africa  Extrapolation to higher CD4 counts  ART initiation may be underreported  Not informative of patients not yet diagnosed

24. Boston University Slideshow Title Goes Here Additional policy options exist  We assessed the simplest implementation of treat all  Eliminate CD4 eligibility criteria and change nothing else  Demand creation  Cash incentives to initiate. Ethical issues.  Information and counseling on benefits of early ART.  Supply-side interventions to lower barriers  Same day ART initiation. (Rosen et al. PLOS Med 2016, 97% ART | linked)  Same day enrollment, even if pills are not dispensed  Case management / accompaniment. (van Rooyen et al. 2013, 80% ART)

25. Boston University Slideshow Title Goes Here Conclusions  Eliminating CD4 thresholds will have benefits for those patients induced to initiate ART and for society.  However, the population induced to start is relatively small.  Guideline change will be affordable, but the effects modest.  Removing CD4 criteria alone, without improving HIV testing, linkage, and initiation procedures will not achieve South Africa’s 90-90-90 targets.

26. Boston University Slideshow Title Goes Here Thank you and acknowledgments  Africa Centre staff and colleagues  Patients and providers  National Department of Health  Funders  NIH (NIMH)  PEPFAR  USAID

27. Boston University Slideshow Title Goes Here National trends in median CD4 count Source: National Health Laboratory Service (NHLS) National HIV Cohort Bor, Nattey, et al. Rising CD4 Counts at Presentation. IAS 2016 Latebreaker Poster Hlabisa sub-district 419

28. Boston University Slideshow Title Goes Here Similar patterns for 200-cell threshold

29. Boston University Slideshow Title Goes Here The good news…  For patients who initiate ART because of the guideline change, we can expect high retention in care (91%) This retention effect is not observed in clinical trials, and suggests that the RCTs may underestimate direct health benefits that would be observed in real world clinical settings. Bor et al. CROI 2016