cape town aids cohort-ctac electronic data sets robin wood desmond tutu hiv centre university of...
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Cape Town AIDS Cohort-CTAC
Electronic Data Sets
Robin Wood
Desmond Tutu HIV Centre
University of Cape Town
Photograph of Masiphumelele
CTAC Data Sets
• Natural history cohort 1984-2000
• Hospital-based ART trials 1996-2003
• Community-based ART programmes 2002-2003
• Web-based ART Register
Natural History Cohort 1984-2000
• Epi-info based– Flow charts of 2088 outpatients– Laboratory, clinical data, OI prophylaxis
• Pros – Doctors like flow charts of CD4 & WHO stages but
not perceived non-useful data!
• Cons– Data transfer, LTFU, missed hospitalisations &
deaths required other data sources
• Outputs– OI frequency, Kaplan-Meier survival
CTAC: Incidence Rates of Opportunistic Infections
0
10
20
30
40
50
60
70
>350 200-350 <200
Inci
denc
e ra
te/1
00 p
atie
nt y
rs
S. bact
Toxo
Cryptosp
CMV
MAI
Crypto
Wasting
KS
Enceph
PCP
HSV
OC
TB
CTAC 2002
CD4+ T-cells/mm3
Hospital-based ART Trials 1996-2003
• Excel spread sheet of CRF data– Lab, clinical events, hospitalisations, deaths
• Pros: – Trial data good quality, variable CD4 entry criteria,
frequent visit intervals
• Cons:– Extracting data laborious
• Outputs:– Changed disease progression– Resource utilisation
TB incidence rates & cases prevented per 100 pys of HAART
0
5
10
15
20
25
CD4 >350 CD4 200-350 CD4<200 WHO3&4
Cas
es /1
00py
s
HAARTNaïve
Cases saved 1.3 9.4 11.3 18.895% CI (0.3-2.9) (3.8-14.3) (6.2-19.1) (13.2-26.1)
WHO 1&2
Badri, Wilson, Wood Lancet 2002
Cumulative Proportion Surviving (Kaplan-Meier)
Complete Censored
NOART Triple
0 200 400 600 800 1000 1200 1400 1600
Time
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Pro
port
ion
of p
atie
nts
stay
ing
in s
tage
1&2
stage1&2, p<0.00001
Progression-free survival of Triple vs NOART: WHO stage 1&2
Category N Patients progressing to
to higher stages
Patients not progressing
To higher stages
P-value
Triple 128 6 (4.7%) 122 (95.3%) <0.0001
NoART 140 52 (37.1%) 88 (62.9%)
Cumulative Proportion Surviving (Kaplan-Meier)
Complete Censored
Triple NOART
0 200 400 600 800 1000 1200 1400 1600 1800 2000 2200
Time
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Pro
port
ion
of p
atie
nts
stay
ing
in s
tage
3
Triple vs NOART, stage 3, p<0.001
Progression-free survival of Triple vs NOART: WHO stage 3
Category N Patients progressing to higher stages
Patients not progressing to higher stages
P-value
Triple 85 13 (15.3%) 72 (84.7%) 0.014
No ART 155 46 (29.7%) 109 (70.3%)
Cumulative Proportion Surviving (Kaplan-Meier)
Complete Censored
Triple NOART
0 200 400 600 800 1000 1200 1400 1600 1800
Time
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Pro
port
ion
of p
atie
nts
stay
ing
in s
tage
4
Triple vs NOART, p=0.009stage 4,
Progression-free survival of Triple vs NOART: WHO stage 4
Category N Patients progressing
to higher stages
Patients not progressing
to higher stages
P-value
Triple 35 4 (11.4%) 31 (88.6%) 0.19
NoART 142 30 (21.1%) 112 (78.9%)
Days/yr (95% CI) OR (95% CI) AV cost PY (95% CI)
WHO Stages 1&2
HAART 0.7 (0.55-0.82) 0.2 (0.14-0.27) 525 (392-694)
No ART 4.4 (3.9-4.9) 1 3,351 (2873-3888)
WHO Stage 3
HAART 1.4 (1.25-1.65) 0.13 (0.11-0.15) 1,113 (980-1293)
No ART 10.9 (10.29-11.46) 1 8,512 (8065-8982)
WHO Stage 4
HAART 6.3 (5.58-6.98) 0.4 (0.38-0.49) 4,899 (4374-5471)
No ART 14.6 (13.81-15.33) 1 11,412 (10824-12016)
HAART impact on hospitalisation (1995-2000)
Usapho Lwethu Community ART Data sources and follow up
• Patient live in recruitment area & must have attended local HIV clinic for > 6 months
• Household support by “Sizophila monitor”• Schedule 1 NNRTI, schedule 2 PI/r• Single referral hospital • Post mortem is requested on all deaths• Access to national mortality data base via “ID
number”
Community ART Programme 2002-2003
• Sequel database, data capture sheets– Laboratory, clinical, QOL, adherence data
• Pros– Fixed visit schedule, LTFU rate low but deaths
high, data captured on “lap-top”
• Cons– Needs data administrator, active search for
missing data
• Outputs– Programme status reports of CD4, VL, survival etc
Clinical Trials vs Community Clinic
Clinical trials n=299 Community n=103
Median CD4 230 cells/ul 82 cells/ul
WHO stage 3&4 49.8% 92.9%
Treatment
ART Regimen NNRTI 58.2%
PI 39.1%
Triple NRTI 2.7%
NNRTI 100%
Results at 16 weeks
VL<400 copies/ml 75.5% (CI 71-80) 94.2% (CI 88-100)
LTFU 5 1
Deaths 2 (0.69%) 7 (6.8%)
Scheduled Clinic Hours
0
10
20
30
40
50
60
70
0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 104 108
Weeks
Monthly drug costs of d4T, 3TC, EFV in study period from Sept 02-May 03
0
200
400
600
800
1000
1200
1400
Initial 4 months 8 months
Ran
d EFV3TCd4T
$159
$73
$41
US$ cost calculated @ R8 per $
Proportional Costs for 250 Patients
48%32%
18% 2%
DrugStaffMonitoringSafety
Cost per patient R8856 per annum
Aerial Photograph of Masiphumele
Pilot National ART Register
• Web-based minimum data from ART programme linked to drug supply– ID number– Clinical stage
– Current drug prescriptions • Linked to laboratory & pharmacy data
– CD4 & Viral load monitoring– Drug monitoring
Proposed Register Outputs
• Patient retention, number on Rx, LTFU and discontinuing
• Drug switching patterns• Time to first failure (MTCT exposure?)• Survival (benefit if compare with natural
history model!)• Drug accountability, dispensing to patients &
“leakage”• Laboratory outcomes CD4/viral suppression
at time-points, resistance
ACKNOWLEGEMENTS FUNDING AGENCIES
NIH Cipra-SA BMS “Secure the Future” Foundation Hannan Crusaid Trusts Heiser Foundation Doris Duke Foundation
UCT AIDS COHORT-CTACMotasim Badri, Desmond Tutu HIV Centre, UCTEduard Beck, McGill University, Montreal, CanadaLinda-Gail Bekker, Desmond Tutu HIV Centre, UCTGary Maartens, Dept of Medicine, Groote Schuur Hospital, UCTKwesi Matoti, PAWC GugulethuCatherine Orrell, Desmond Tutu HIV Centre, UCTLarissa Reader, Desmond Tutu HIV Centre, UCTEve Sabotski, PAWC South PeninsulaDouglas Wilson, Dept of Medicine, Somerset Hospital, UCT
Sizophila Team April 2003
Photograph of Sizophila Team