Transcript ISSUES IN COMPLIANCE1

Antiretroviral Treatment Monitoring: A
Canadian Case Example
Robert Hogg, PhD
BC Centre for Excellence in HIV/AIDS
Dept. of Health Care and Epidemiology
University of British Columbia
British Columbia
HIV/AIDS Drug Treatment Program
•
In BC antiretrovirals have been centrally
distributed free of charge to eligible HIV+
individuals since 1986
•
In October 1992, the HIV/AIDS Drug Treatment
Program became the responsibility of the BC
Centre for Excellence
•
Ever enrolled over 6,500 and 2,800 currently
on therapy
Monitoring and Evaluation
•
Patient, Physician and geographical characteristics
•
Antiretroviral therapy dispensing information
•
Sociodemographic and adherence-related data
•
Clinical and laboratory data, including CD4 and plasma
viral load
•
Morbidity and mortality data updated through linkages
•
Antiretroviral resistance
•
Adherence measures
Percent of persons first starting antiretroviral
therapy on NNRTIs (Aug 1998 to Jan 2003)
Nevirapine use in British Columbia
(Jan 2002 to Jan 2003)
Percent frequency distribution of initial antiretroviral
regimens in British Columbia (1993-2001)
100
90
80
70
60
50
40
30
20
10
0
1
2
3
4
1993 1994 1995 1996 1997 1998 1999 2000 2001
N
614
317
398
963
764
456
397
Therapy Start Time (year)
291
284
ARV
ARV
ARV
ARV
Progression to AIDS/Death
30
25
No therapy
20
Mono-therapy
15
Dual-therapy
10
Triple therapy
5
0
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Months
JAMA 1998 & CMAJ 1999
Deaths per 1,000 pts ever on therapy
Updated from Hogg et al, Lancet, 1999
140
3
CD4 (/mm )
Number of Deaths
120
0 to 100
100 to 350
350 to 500
above 500
100
80
60
40
20
0
2001-1
2000-3
2000-1
1999-3
1999-1
1998-3
1998-1
1997-3
1997-1
1996-3
1996-1
1995-3
1995-1
1994-3
1994-1
Year
By Quarters
Drug Costs
Cost:
1992/93:
$500,000 US
2003/3004: $30,000,000 US
Antiretroviral cohorts
International (PLATO, ART collaborative study)
IDU (BART)
First start (HOMER)
STI
Mega HAART
Women
HAART Observational Medical
Evaluation and Research (HOMER) Study
•
Population-based study of HIV+ men and
women in the Drug Treatment Program
•
Aged 18 years and over
•
Antiretroviral naive
•
First prescribed triple therapy (2 NRTIs and
either a PI or an NNRTI) between August 1,
1996 and September 30, 1999
HOMER
When to start therapy in 2002
Disease Type
Recommendations
<5K
5 to 30 K
> 30 K
Cells/mm3
< 350
Symptomatic
Recommend
350
to 500 3
 200
cells/mm
Recommend
3 Based on CD4 decline, high viral load, patient interest,
> 200>cells/mm
500
adherence potential, and risk of side effects
IAS-USA, JAMA, July 2002
Combined CD4
&
HIV-RNA
groups
Hogg et al JAMA, 2001
100
High CD4
Low HIV-RNA
High HIV-RNA
98
96
94
Intermediate CD4
Low HIV-RNA
High HIV-RNA
92
90
88
86
High CD4: >=200 cells/mm3
Low HIV-RNA: < 100K c/mL (n=416)
High HIV-RNA: >=100K c/mL (n=360)
84
82
80
78
76
74
72
Intermediate CD4:>=50-199 cells/mm3
Low HIV-RNA: < 100K c/mL (n= 97)
High HIV-RNA: >=100K c/mL (n=204)
Low CD4
Low HIV-RNA
High HIV-RNA
Low CD4:< 50 cells/mm3
Low HIV-RNA < 100K c/mL (n= 28)
High HIV-RNA: >=100K c/mL (n=114)
70
0
3
6
9
12
15
18
Time from Start of ARVs (mths)
21
24
CD4 groups stratified by adherence
> 75% Adherent
< 75% Adherent
> 200 cells/mm 3
100
100
95
50 - 199 cells/mm 3
90
85
< 50 cells/mm 3
80
75
70
65
60
55
50
45
40
Probability of Survival (%)
95
Probability of Survival (%)
> 200 cells/mm 3
90
85
80
75
65
60
55
50
45
40
35
35
30
30
0
6
12
18
24
30
Time Since Start of ARVs
36
42
50 - 199 cells/mm 3
70
< 50 cells/mm 3
0
6
12
18
24
30
36
Time Since Start of ARVs
Wood et al. AIDS, 2003
42
Risk of Death by baseline CD4 cell count and adherence
Adherence
CD4
Adjusted
Level
Cell Count
Relative Hazard
(95% CI)
> 75%
> 200
1.0
REF
< 75%
> 200
3.6
(1.7, 7.4)
> 75%
50 - 199
4.5
(2.4, 8.7)
< 75%
50 - 199
9.8
(4.5, 21.3)
> 75%
< 50
6.2
(3.0, 12.6)
< 75%
< 50
35.7
(16.2, 78.9)
*Model was adjusted for physician experience, history of injection drug use,
baseline plasma viral load, age, and AIDS at baseline.
Wood et al. AIDS, 2003
Probability of Survival (%)
NNRTI vs. PI: Time to Death
100
98
96
94
92
90
88
86
84
Log-rank
p = 0.252
Initial Regimen
82
80
78
76
74
72
70
NNRTI
PI
0
6
12
18
24
30
36
Time from Start of ARVs (months)
Hogg et al., IAS, 2002
Probability of Adding/Switching ARV (%)
Time to Switching Therapy
80
70
2 Nuc + PI
(N=983)
2 Nuc + NNRTI (N=439)
60
50
log rank p<0.001
40
30
20
10
0
0
6
12
18
24
Time from Start of ARVs (months)
30
36
Probability of Detecting Resistance (%)
Time to First Simultaneous Resistance to Antiretrovirals
40
>=1 Class
35
>=2 Classes
30
>=3 Classes
25
4 Classes
20
15
10
5
0
0
6
12
18
24
Time from Start of Antiretrovirals(months)
>=1C
>=2C
>=3C
4C
N=
N=
N=
N=
1219
1219
1219
1219
873
932
954
959
743
822
861
873
621
702
752
772
488
559
602
623
Harrigan et al., IAS, 2003
Probability of Detecting Resistance (%)
Time to First Detection of Resistance to Each Class of Antiretrovirals
40
Lamivudine
35
NNRTI
30
NRTI (non-3TC)
25
PI
20
15
10
5
0
0
6
12
18
24
Time from Start of Antiretrovirals(months)
(Lamiv)
(NNRTI)
(NRTI)
(PI)
N=
N=
N=
N=
1219
1219
1219
1219
899
937
935
947
783
826
839
848
662
712
730
741
528
570
580
591
Harrigan et al., IAS, 2003
Donald Rumsfeld
Clarifying US Policy on the war on terror
Newsweek, March 10, 2003
“There are known knows. These are things we know
that we know. There are known unknowns. That is
to say, there are things that we know we don’t know.
But these are also unknown unknowns. There are
things we don’t know we don’t know.”
Human security?
Impact of Various ART Strategies in South Africa
Based on E Wood and P Braitstein et al. Lancet 2000 June 17;vol 355:2095-2100
Life Expectancy at Birth
50
25% Antiretroviral Therapy Use
49
48
No Therapy
47
46
1999
2000
2001
2002
2003
2004
2005 Year
Acknowledgements
Julio Montaner
Benita Yip
Keith Chan
Evan Wood
Michael O’Shaughnessy
Paula Braitstein
Richard Harrigan
Nada Gataric
Michael Smith Foundation for Health Research
The Canadian Institutes of Health Research
BC Centre for Excellence in HIV/AIDS