1. Modified Directly Observed Therapy for First Virologic Failure: ACTG A5234 PI Dr A Chisada Presenter: Dr W Samaneka MBChB, MSc UZ-UCSF ARD 17 April 2015

2. Sustained and consistent adherence is a key factor for durable ART success 2nd line therapy is typically more complex and expensive than 1 st line Conventional DOT is logistically challenging Enhanced partner support may benefit patients with prior treatment failure. Background

3. Main Objective  To test whether a partner-based modified DOT (mDOT) intervention would result in higher rates of virologic suppression compared with standard of care after first-line treatment failure

4. Methods Study duration: Apr 2009 – Sep 2011 Confirmed virologic failure on 1st line Identifiable mDOT partner (family, friend, etc.) 1:1 allocation to mDOT and standard of care 2nd line: lopinavir/r (400 mg/100 mg) BID + TDF/FTC (300 mg/200 mg) qD Brazil, Botswana, Haiti, Peru, SA, Uganda, Zambia, Zimbabwe

5. End Points Primary efficacy endpoint Confirmed Virologic Failure HIV RNA>400 cpm by week 48 Secondary endpoints Confirmed virologic failure HIV RNA>400 cpm by week 24 Adherence measured using electronic monitors[MEMS] summarized quarterly as % of doses taken

6. mDOT Intervention Design Single training session of mDOT partner (1.5 hrs)  Drug regimen  Adherence &handling missed doses  Side effects  Examples of +ve and –ve social support  Documentation of observed doses  How and when to contact site for help  Provision of airtime (buddie)  Duration of active phase: 24 weeks (total follow up 52 wks)

7. Participant Flow Diagram

8. RESULTS Baseline Characteristics CharacteristicmDOTSOC n =129N=128 Median age (IQR)38 y (34,44)37 y (33, 45) Female sex62 (48%)65 (51%) Black race101 (78%)103 (80%) Hispanic ethnicity27 (21%)25 (20%) Prior rx duration153 wks144 wks (IQR)(82, 230)(89, 245) Entry CD4 (median)164 c/mm3201 c/mm3 (IQR)(91, 250)(97, 292) Nadir CD4 (median)122 c/mm3109 c/mm3 (IQR)(37, 187)(45, 202) HIV RNA (median)4.2 log cpm (IQR)(3.8, 4.9)

9. Endpoints by Study Arm Fishers Exact Points for VF,Wicoxon Rank Sum test for Adherence Endpoints mDOTSOCP-value Endpointn =129N = 128 VF wk 4834 (26%)23 (18%)0.13 VF wk 2424 (19%)17 (13%)0.31 Adherence Q195%96%0.38 Adherence Q291%94%0.30 Adherence Q390%93%0.17 Adherence Q490%93%0.36

10. Virologic suppression ≤ 400 At all time points after week 12 undetectable VL was higher in SOC, however not significant Week 48, 75% (CI 67-83) in mDOT and 82% in SOC (CI 74-89) had VL ≤ 400, (p=0.37) No sig diff between groups at week 24; p=0.18

11. Virologic Suppression (HIV-RNA ≤ 400 cpm)over time

12. Conclusion mDOT had no significant impact on virologic failure  High rate of suppression in both arms mDOT had no significant impact on adherence  High rate of adherence in both arms Other interventions still need to be tested in this setting

13. Although mDOT intervention not successful findings are encouraging > high rates of virologic success on second line therapy in RLS

14. Acknowledgements Sponsors – NIAID - Abbott Laboratories - Gilead Sciences Study participants + partners CAB CRS Leader- Prof JG Hakim ACTG site staff UZ-UCSF