Twenty-four month outcome of the PASER cohort: what happens to patients failing ART?

Pascale Ondoa

Sonia Boender

PASER studies in figures

2755 patients initiating 1st line followed up for at least 24 month

253 patients enrolled at second line switch followed up for 24 months

6 countries13 clinical sites

1st line 2nd line

Baseline

Month 12

Month 24

>month 48

Switch

Switch

Switch

Month 12 and month 24

outcomes of 1st and 2nd line

ART

2755 start 1st 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 2nd line

•20 deaths•84 LTFU•38 Transferred out•7 Stop PASER/ART•53 switch to 2nd line

•85 miss VL results• 175 (8.3%) with VF

•110 miss VL•171 (10.7%) with VF

Month 12 and month 24 outcomes: 1st versus 2nd line

12

253 start 2nd line

•217 (85.7%) alive active in the cohort still on 2nd line after 12M

•195(77.0%) alive active in the cohort still on 2nd

•line after 24 M

•11 deaths•20 LTFU•5 transfer out

•5 deaths•10 LTFU•4 Transferred out•3 switch to 3nd line

•7 miss VL results• 23 (10.9%) with VF

•14 miss VL results• 27(14.9%) with VF

12

24 24

HIVDR mutations in patients failing 1st line at month 12 and 24 (overall).

All mu-tations

NRTI Any TAM K65R Y115F M184V Any NNRTI

K103N V106M Y188H Y188L G190A Any PI0

10

20

30

40

50

60

70

80

90

%Month 12

%Month 24

Mutations

Pe

rce

nta

ge

of

mu

tati

on

s

N=144

N=144

Number of mutation/sequences increases from 2.16 (month 12) to 2.64 (month 24).Prevalence comparable between the 13 sites

Effect of baseline resistance at initiation of 1st line ART on 12 and 24 months outcomes – excluding participants not on standard 1st line

2745 participants

initiating 1st -line ART

2562 receivedfully 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

HIVDR mutations in patients failing 2nd- line ART at month 12 and month 24

All mu-tations

NRTI Any TAM K65R Y115F M184V Any NNRTI

K103N V106M Y188H Y188L G190A Any PI0

10

20

30

40

50

60

70

80

%Month 12

%Month 24

Mutations

Perc

enta

ge o

f H

IVD

R m

uta

ion

N=18

N=21

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 1st line profile.

Effect of resistance at switch to 2nd line ART on 12 and 24 months outcomes – excluding participants with PI exposure

243 participants switched to 2nd-line ART

109 receivedfully 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 2nd-line ART

192 (79%) participants remained in

care, on 2nd-line ART

14 (16%) VF

15 (13%) VF

11 (15%) VF

16 (15%) VF

p=0.586 p=0.897

Key messages of month 12 and 24 outcome

High rates of viral suppression (>70%) and resistance profiles indicate that current 1st and 2nd 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 1st and 2nd line.

Prevalence of TAMS and PI especially increase from month 12 to month 24 in patient failing 2nd-line.

Initiating a partially active 1st but not 2nd line regimen is associated with a higher odds for VF at month 12 and 24

What happens to patients

failing ART in the course

of PASER?

Patient failing VL>1000

cp/mL

Switch to 2nd line before or @ next

visitRe-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 ?

PASER sites represent very different settings that can influence the management of virological failure

Country Site SectorNumber 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/LTH PFP 61 No d No Yes Clients 03/07

ZA/KAR NGO 220 Yes Yes No CIDRZ/PEPFAR 03/07

ZA/CHC FBO 196 Yes Yes No CHAZ/PEPFAR 05/07

SA

SA/MMH PFP 767 No d Yes Yes Clients 05/07

SA/TLC Public 933 Yes Yes Yes MOH/USAID 09/07

SA/ACC NGO 825 Yes Yes Yes USAID/PEPFAR 11/07

ZIM ZI/CON NGO 109 Yes Yes No SACI/SDC 09/08

UG

UG/JCR Public 134 Yes Yes Yes USAID/PEPFAR 01/08

UG/JFP Public 693 Yes Yes Yes USAID/PEPFAR 01/08

UG/MBA Public 603 Yes Yes Yes USAID/PEPFAR 02/08

KEKE/CRH Public 627 Yes Yes No MOH/USAID 11/07

KE/MAT FBO 200 Yes Yes No PEPFAR 02/08

NI NI/LUT Public 344 Yes Yes Yes MOH/PEPFAR 09/08

Adapted from Hamers et al, 2010

What becomes of patients failing between month 12 and month 24?

198 virological failures at month 12 M12

M24

17%

19%37%

19%switch to 2nd or 3rd linenot switch and re-supressedStill failing at month 24death, LTFU, trasfer out

40% of switch in sites where VL is not available

52% of persisting VF in sites where VL testing is available

What is the VL of patients that are switched to next line in the course of PASER?

76,4%

23,6%

Virological failure at time of switch

VL>1000 cps/mL

23.6% of switches are unnecessary

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.

Thank you