1. Twenty-four month outcome of the PASER cohort: what happens to patients failing ART? Pascale Ondoa Sonia Boender

2. PASER studies in figures 2755 patients initiating 1 st line followed up for at least 24 month 253 patients enrolled at second line switch followed up for 24 months 6 countries 13 clinical sites 1 st line 2 nd line Baseline Month 12 Month 24 >month 48 Switch

3. Month 12 and month 24 outcomes of 1 st and 2 nd line ART

4. 2755 start 1 st line 2186(79.3%) alive active in the cohort still on first line after 12M 1984(72.0%) alive active in the cohort still on first line after 24 M 200 deaths 253 LTFU 80 Transfer out 10 Stop PASER/ART 26 early switch to 2 nd line 20 deaths 84 LTFU 38 Transferred out 7 Stop PASER/ART 53 switch to 2 nd line 85 miss VL results 175 (8.3%) with VF 110 miss VL 171 (10.7%) with VF Month 12 and month 24 outcomes: 1 st versus 2 nd line 12 253 start 2 nd line 217 (85.7%) alive active in the cohort still on 2 nd line after 12M 195(77.0%) alive active in the cohort still on 2 nd line after 24 M 11 deaths 20 LTFU 5 transfer out 5 deaths 10 LTFU 4 Transferred out 3 switch to 3 nd line 7 miss VL results 23 (10.9%) with VF 14 miss VL results 27(14.9%) with VF 12 24

5. HIVDR mutations in patients failing 1 st line at month 12 and 24 (overall). Number of mutation/sequences increases from 2.16 (month 12) to 2.64 (month 24). Prevalence comparable between the 13 sites

6. Effect of baseline resistance at initiation of 1 st line ART on 12 and 24 months outcomes – excluding participants not on standard 1 st line 2745 participants initiating 1 st - line ART 2562 received fully active regimen (GSS ≥ 3) 158 received partially active regimens (GSS < 3) Baseline 12 months 24 months 2084 (75.9%) participants remained in care, on 1st-line ART 1859 (67.7%) participants remained in care, on 1st-line ART 149 (7.5%) VF 22 (21.2%) VF 157 (8.8%) VF 14 (19.4%) VF P<0.001 P=0.002

7. HIVDR mutations in patients failing 2 nd - line ART at month 12 and month 24 Overall prevalence of mutations at month 12 (55%) is relatively low. number mutations/sequence= 2.66 (month 12) and 2.87 (month 24). Prevalence of TAM and PI is higher than at baseline and than 1 st line profile.

8. Effect of resistance at switch to 2 nd line ART on 12 and 24 months outcomes – excluding participants with PI exposure 243 participants switched to 2 nd -line ART 109 received fully active regimen (GSS ≥ 3 or VL< 1000) 132 received partially active regimens (GSS < 3) Baseline 12 months 24 months 213 (88%) participants remained in care, on 2 nd -line ART 192 (79%) participants remained in care, on 2 nd -line ART 14 (16%) VF 15 (13%) VF 11 (15%) VF 16 (15%) VF p=0.586p=0.897

9. Key messages of month 12 and 24 outcome High rates of viral suppression (>70%) and resistance profiles indicate that current 1 st and 2 nd line regimen do not need to be changed. Relatively similar HIVDR mutation profiles at month 12 and 24. Prevalence of mutations slightly increase over time in both 1 st and 2 nd line. Prevalence of TAMS and PI especially increase from month 12 to month 24 in patient failing 2 nd -line. Initiating a partially active 1 st but not 2 nd line regimen is associated with a higher odds for VF at month 12 and 24

10. What happens to patients failing ART in the course of PASER?

11. Patient failing VL>1000 cp/mL Switch to 2 nd line before or @ next visit Re-suppression/or not(?) Not switched but suppressed at next visit Adherence counseling Viral blip? Not switched, still failing at next visit Accumulation of DR mutations and worsening of clinical status ? Attrition ? Identified ?

12. PASER sites represent very different settings that can influence the management of virological failure CountrySiteSector Number of patients per staff b Free care c Patient tracing e HIV viral load available Main funding source Month/ year of study initiation ZAM ZA/LTHPFP61No d NoYesClients03/07 ZA/KARNGO220Yes NoCIDRZ/PEPFAR03/07 ZA/CHCFBO196Yes NoCHAZ/PEPFAR05/07 SA SA/MMHPFP767No d Yes Clients05/07 SA/TLCPublic933Yes MOH/USAID09/07 SA/ACCNGO825Yes USAID/PEPFAR11/07 ZIMZI/CONNGO109Yes NoSACI/SDC09/08 UG UG/JCRPublic134Yes USAID/PEPFAR01/08 UG/JFPPublic693Yes USAID/PEPFAR01/08 UG/MBAPublic603Yes USAID/PEPFAR02/08 KE KE/CRHPublic627Yes NoMOH/USAID11/07 KE/MATFBO200Yes NoPEPFAR02/08 NINI/LUTPublic344Yes MOH/PEPFAR09/08 Adapted from Hamers et al, 2010

13. What becomes of patients failing between month 12 and month 24? 198 virological failures at month 12 M12 M24 52% of persisting VF in sites where VL testing is available

14. What is the VL of patients that are switched to next line in the course of PASER? 23.6% of switches are unnecessary

15. Conclusions VL testing availability does not seem to translate into optimal use of laboratory information for the management of ART. Barriers to the utilization of laboratory tools need to be identified and mitigated as technology is being scaled up.

16. Thank you