Post on 05-Jan-2016
description
Long term follow-up on ARV treatmentOutcomes and challenges at 48 months in
Khayelitsha ,South Africa
Provincial Government of the Western Cape
Infectious Disease Epidemiology Unit, University of Cape Town
Médecins Sans FrontièresMSF Scientific day,June 1st 2006
- the experience in Khayelitsha- the experience in Khayelitsha
Khayelitsha townshipKhayelitsha township• Peri-urban township ~
500.00 inh.
• PMTCT started in 1999, HIV clinics in 2000 and ARV in 2001
• HIV antenatal rate ~ 30 % and TB incidence at 1750/100.000
• TB/HIV co-infetion rate at 72%
• ~ 8000 patients on active file including 3800 patients on ARV
Khayelitsha Antenatal HIV PrevalenceKhayelitsha Antenatal HIV Prevalence 1999-20051999-2005
10%
15%
20%
25%
30%
35%
J an-Mar
1999
Oct-Dec J ul-Sep Apr-J un J an-Mar
2002
Oct-Dec J ul-Sep Apr-J un J an-Mar
2005
Oct-Dec
Mean Prevalence (95 % CI)
Impact of the scaling up strategyImpact of the scaling up strategy
Number of new patients started on ART per year
Median CD4 count on starting (IQR) by year of starting
84237
419
1138
1831
0
500
1000
1500
2000
2001 2002 2003 2004 2005
48
7385
105
41.5
0
20
40
60
80
100
120
140
160
180
2001 2002 2003 2004 2005
Children 0-14 years Children 0-14 years ART initiation by yearART initiation by year
17 2038
531517
32
48
3
1
0
20
40
60
80
100
120
2001 2002 2003 2004 2005
Nu
mb
er
sart
ed
on
AR
T
boys girls
Vertical transmission rate measured at 8.8 % (.PCR survey 2004, n=500)
Mortality at 3,6,12 and18 months Mortality at 3,6,12 and18 months according to year ART initiatedaccording to year ART initiated
0.0%
2.0%
4.0%
6.0%
8.0%
10.0%
12.0%
2001 2002 2003 2004 2005
Perc
ent d
ied 3 m
6 m
12m
18m
Median Cd4 cells counts at different time Median Cd4 cells counts at different time points points
Khayelitsha 2001-1005 n=3152
81
229271 239
303372 380
460
0
100
200
300
400
500
600
CD
4 ce
ll co
unt
chan
ge (
med
ian
IQR
)
Proportion of undetectable VL Proportion of undetectable VL ( < 400 copies/ml) ( < 400 copies/ml)
Khayelitsha 2001-1005 n=3152
0%
20%
40%
60%
80%
100%
0 3 6 12 18 24 30 36 42 48
Months on ART
Retention in care at 48 monthsRetention in care at 48 months(on first and second lines)(on first and second lines)
60%
65%
70%
75%
80%
85%
90%
95%
Months on ART
93% 90.20% 86.60% 84% 80.5% 80.6% 78.3% 77.6% 75.6%
3 6 12 18 24 30 36 42 48
Lost to follow-up by time period according to Lost to follow-up by time period according to
year ART initiatedyear ART initiated
0 04
11
35
0 04
20
31
0
5
10
15
20
25
30
35
40
2001 2002 2003 2004 2005
Num
bers
LTF
3 months 6 months
Substitutions due to toxicity by drugSubstitutions due to toxicity by drug
nChanged by 36 months (%, 95% CI)
d4T 1228 1065 471 113 18 9 5 16.5 (12.0-22.6)AZT 639 497 442 417 306 205 132 8.3 (6.3-10.9)NVP 977 828 385 129 104 89 63 7.4 (5.4-10.1)EFV 967 790 558 423 245 139 81 3.1 (1.8-5.5)
0.00
0.05
0.10
0.15
0.20
0 6 12 18 24 30 36Duration on drug in months
Kaplan-Meier failure estimate
d4T
AZT
NVP
EFV
Pro
por
tion
subs
titut
ed d
ue t
o to
xici
ty
13th Conference on Retroviruses and Opportunistic Infections, Denver 2006
Causes of toxicity-driven substitutions on D4TCauses of toxicity-driven substitutions on D4T
Lactic acidosis / symptomatic hyperlactataemia
0.00
00.
025
0.05
00.
075
0.10
0
0 6 12 18 24 30 36
Duration on stavudine in months
Kaplan-Meier failure estimate
Peripheral neuropathy
Other toxicities incl. lipodystrophy
Pro
por
tion
subs
titut
ed d
ue t
o to
xici
ty
Hyperlactataemia/LA 1228 1074 484 118 20 11 6 8.7 (5.3-14.0)Peripheral Neuropathy 1228 1068 486 120 19 9 5 6.4 (4.0-10.2)
Other 1228 1073 495 123 21 11 6 1.7 (0.6-4.6)
nChanged by 36mo
(%, 95% CI)Reason for subst.
Combined 1228 1065 471 113 18 9 5 16.5 (12.0-22.6)
13th Conference on Retroviruses and Opportunistic Infections, Denver 2006
Rate of substitutions due to symptomatic Rate of substitutions due to symptomatic hyperlactataemia/lactic acidosishyperlactataemia/lactic acidosis
30 2
60
17
81
44
316
0
100
200
300
400
500
Every
one
< 6
mon
ths
>= 6
mon
ths
Men
>=
6 m
onth
s
Wom
en >
= 6
mon
ths
Wom
en<
75kg
, >=
6 m
onth
s
Wom
en >
= 75
kg, >
= 6
mon
ths
Rat
e pe
r 10
00py
13th Conference on Retroviruses and Opportunistic Infections, Denver 2006
Proportion of patients on second lineProportion of patients on second line
4.2%
0.6%
11.0%
17.8%
0%2%4%6%8%
10%12%14%16%18%20%
12 (1419) 24 (500) 36 (209) 48 (56)
Months on ART (n=)
Cu
m %
on
2n
d l
ine
• Regimen change on virological failure defined as 2 consecutive measures > 5.000 copies/ml
• Each complete regimen interruption (for AE, CI or hospitalisation) results in increased risk of virological failure (AHR 3.2 [95% CI 2.0-5.1], p<0.001), controlled for baseline CD4 count.
Needs coverage Needs coverage
• Inclusion rate needs to reach 3200 new patients/year by 2010
• Cumulative :3800 patients on HAART now while estimated 15.000 patients by 2010
• Based on existing 3 clinics model, > 5000 patients/clinic by 2010
• Based on existing doctor/nurses ration, unfeasible0
500
1000
1500
2000
2500
3000
3500
19
85
19
87
19
89
19
91
19
93
19
95
19
97
19
99
20
01
20
03
20
05
20
07
20
09
20
11
20
13
20
15
Demand at 70%Started ART
Source : ASSA model 2003
Monitoring and evaluation : a triangular relation between Monitoring and evaluation : a triangular relation between clinic staff , Cape Town University and MSFclinic staff , Cape Town University and MSF
Real time clinical records capture in each clinic fter
each visit (dedicated clerk)
Data cleaning / integration of lab records
Monthly activity report
Quarterly outcomes cohort report
Retrospective database analysis for specific operational research
questions
Daily patient bookings
Daily missed appointment and weekly defaulters list
Clinic staff University of Cape Town /MSF epidemiologist
Conclusions Conclusions
• More than 75 % of initial patients are still in care at 48 months including 18 % on 2nd line :while numbers starts to grow,there is no affordable and patient friendly second line available
• While scaling up , challenges of managing large teams and initial signs of staff burn require innovative radical solution to cope with projected workload by 2010
• Long term D4t related toxicity requires an urgent revision of our guidelines
• Universal access is possible in such high prevalence setting but tight monitoring together with reactive management lines are essential for ongoing adaptation of service with such explosive growth
• Partnership for operational research in with UCT had a major influence on national policies and guidelines .It has improved MSF operational research standards and made results acceptable in a politically sensitive context
AcknowledgementsAcknowledgements• Patients and staff at HIV clinics
• Monitoring and evaluation team : University of Cape Town and MSF (Andrew Boulle, Katherine Hildebrand, Washifa Abrahams)
• ARV task team, Western Cape Department of Health