1. Feasibility and acceptability of an antiretroviral treatment as prevention (TasP) intervention in rural South Africa Results from the ANRS 12249 TasP cluster-randomised trial C. Iwuji, J. Orne-Gliemann, F. Tanser, R. Thiébaut, J. Larmarange, N. Okesola, ML. Newell, F. Dabis for the ANRS 12249 TasP study 20th International AIDS Conference 2014

2. Background and objectives

3. Plasma HIV viral load: primary determinant of the risk of HIV transmission (Quinn NEJM 2000) Good evidence that ART reduces sexual transmission of HIV (Cohen NEJM 2011, Tanser Science 2013) What is the effectiveness of using ART as prevention (TasP) at the population level in an HIV hyper- endemic community in rural KwaZulu-Natal? ART as prevention

4. Objectives of the ANRS TasP trial Phase 1: March 2012-June 2014  To estimate the feasibility and acceptability of the TasP intervention at community and health facility levels  To validate and update the parameters of the model used to estimate the impact of the intervention and sample size: uptake of HIV testing, HIV prevalence, linkage to care upon HIV diagnosis, ART uptake and internal migration Overall: March 2012-June 2016  To evaluate the effect of ART initiated immediately after HIV diagnosis, irrespective of CD4 count criteria, on HIV incidence in the general population in the same setting Phase 1 2014 2012 2016 Phase 2

5. Design and methods (Registration number in http://clinicaltrials.gov/: NCT01509508)

6. Study design Cluster randomized trial protocol: (Iwuji C et al. Trials 2013) Sample size calculations and assumptions  1,000 eligible participants/cluster; 22,000 participants in the 22 clusters implemented in full trial  80% power to show a 34% reduction in cumulative incidence Home-based HIV-testing Control Treat all HIV+ individuals according to South African guidelines (<=350 CD4,WHO stage 3 or 4) Intervention Treat all HIV+ individuals regardless of CD4 count and clinical stage

7. TasP trial area Sub-district : Hlabisa Region : KwaZulu-Natal 1 430 Km 2 228,000 Zulu speaking people HIV prevalence is 24% 10 clusters (4 then 6) in phase 1 An additional 12 clusters in phase 2

8. Trial procedures Homestead identification (GPS)

9. Trial procedures Homestead identification (GPS) Homestead visit 1.Head of household verbal consent 2.Registration of individuals Inclusion criteria Resident member of a household 16 years or older Able to give informed consent Exclusion criteria Untreated psychiatric disorder Neurological impairment

10. Trial procedures Homestead identification (GPS) Homestead procedures 1.Household assets questionnaire 2.Individual questionnaire 3.DBS sample, rapid HIV testing 4.TasP card Homestead visit 1.Head of household verbal consent 2.Registration of individuals

11. Trial procedures Homestead identification (GPS) Homestead procedures 1.Household assets questionnaire 2.Individual questionnaire 3.DBS sample, rapid HIV testing 4.TasP card Homestead visit 1.Head of household verbal consent 2.Registration of individuals Referral to TasP clinics Repeat HIV test 6 mths later HIV + HIV - TasP clinic - One per cluster (45mn walk max) - HIV treatment and care - Study questionnaires

12. Results

13. Trial enrolment flowchart as of 22 nd of May 2014

14. 95% of contacted individuals completed study questionnaire

15. Trial enrolment flowchart as of 22 nd of May 2014

19. Repeat HIV ascertainment Ascertainment = rapid test performed (with a valid result) or if individual reported to the fieldworkers already knowing being HIV+

20. ART coverage at referral (among all HIV+ referred) ART coverage at referral: 39.7% (1,021 / 2,570) [95% CI: 37.4% - 42.1%]  Control clusters: 40.8% (583 / 1,430) [37.6 - 44.0]  Intervention clusters: 38.4% (438 / 1,140) [36.5 - 40.4]

21. ART initiation (among those not on ART at referral, denominator includes those not in care) ART initiation after referral: 33.9% (525 / 1,549) ART initiation after referral (individuals observed at least one year): 48.0% (300 / 625)  Control clusters: 38.9% (107 / 275)  Intervention clusters: 55.1% (193 / 350)

22. ART initiation (among those not on ART at referral who are linked to TasP clinics) ART initiation after referral: 64.2% (386 / 601)  Control clusters: 45.2% (142 / 314)  Intervention clusters: 85.0% (244 / 287) For those with CD4 > 350 cells/mm 3 : 80.1% (129 / 161)

23. Model parameters versus observed estimates Protocol v2.0Observation phase 1 (2012-14) ParameterAssumptionsIndicatorValues (%) [95% CI] ART reduction in infectiousness 90% -- Proportion with partners in opposite arm 10% -Not yet available

24. Protocol v2.0Observation phase 1 (2012-14) ParameterAssumptionsIndicatorValues (%) [95% CI] ART reduction in infectiousness 90% -- Proportion with partners in opposite arm 10% -Not yet available HIV test offer among those registered 90%Contact rate per calendar round (/CR) 67% [63-71] Test acceptance among those offered 80%HIV ascertainment rate/CR 77% [74-80] Model parameters versus observed estimates

25. Protocol v2.0Observation phase 1 (2012-14) ParameterAssumptionsIndicatorValues (%) [95% CI] ART reduction in infectiousness 90% -- Proportion with partners in opposite arm 10% -Not yet available HIV test offer among those registered 90%Contact rate per calendar round (/CR) 67% [63-71] Test acceptance among those offered 80%HIV ascertainment rate/CR 77% [74-80] Linkage to care upon diagnosis among those accepting the test 70%Entry into care within 6 months among individuals not in care 48% [44-52] Proportion of all HIV+ on ART in end 2011 39%ART coverage at the beginning of the trial 39% [36-42] Model parameters versus observed estimates

26. Protocol v2.0Observation phase 1 (2012-14) ParameterAssumptionsIndicatorValues (%) [95% CI] ART reduction in infectiousness 90% -- Proportion with partners in opposite arm 10% -Not yet available HIV test offer among those registered 90%Contact rate per calendar round (/CR) 67% [63-71] Test acceptance among those offered 80%HIV ascertainment rate/CR77% [74-80] Linkage to care upon diagnosis among those accepting the test 70%Entry into care within 6 months among individuals not in care 48% [44-52] Proportion of all HIV+ on ART in end 2011 39%ART coverage at the beginning of the trial 39% [36-42] HIV prevalence in end- 2011 (15 years +) 24%HIV prevalence (first DBS) 30% [29-31] HIV incidence in end 2011 (15 years +) 2.4 / 100 PYObserved HIV incidence 2.35 / 100 PY [1.40-3.31] Model parameters versus observed estimates

27. Conclusions High community acceptance of the trial with 95% of contacted individuals participating High initial and repeat HIV ascertainment rates High initial ART coverage Linkage to care amongst newly diagnosed HIV + takes time High ART uptake rates amongst those linked to TasP clinics Interventions to improve linkage to care being scaled-up Phase 2 started June 2014

28. Acknowledgements Trial participants Africa Centre staff Traditional Authority Department of Health, South Africa Merck/Gilead ANRS 12249 Study Group: Till Bärnighausen, Sylvie Boyer, Alexandra Calmy, François Dabis (co-PI), Rosemary Dray-Spira, Ken Freedberg, John Imrie, Collins Iwuji (Coordinator South), Sophie Karcher, Joseph Larmarange, France Lert, Richard Lessells, Kevi Naidu, Colin Newell, Marie-Louise Newell (co-PI), Nonhlanhla Okesola, Tulio de Oliveira, Joanna Orne-Gliemann (Coordinator North), Deenan Pillay (co-PI), Bruno Spire, Frank Tanser, Rodolphe Thiébaut, Johannes Viljoen