Treatment as Prevention: HAART Expansion - A Powerful Strategy to Reduce AIDS Morbidity and Mortality and HIV Incidence - World Health ...
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Treatment as Prevention:
HAART Expansion - A Powerful Strategy to Reduce
AIDS Morbidity and Mortality and HIV Incidence
Julio Montaner MD, FRCPC, FCCP, FRSC
Director, BC-Centre for Excellence on HIV/AIDS, Providence Health Care
Professor of Medicine and Head, Division of AIDS, University of British Columbia
President, International AIDS Society
UNAIDS, Geneva, March 24th 2010
British Columbia
Centre for Excellence
in HIV/AIDS
USA - Trends in Annual Rates of Death
Ages 25 to 44
40 Unintentional
Deaths per 100,000 Population
injury
35 Cancer
30
Heart
25 disease
Suicide
20
15 HIV infection
10 Homicide
5 Chronic liver
disease
0 Stroke
82 84 86 88 90 92 94
Diabetes
Year
Harald zur Hausen Françoise Barré-Sinoussi Luc Montagnier
Announced Oct 6th 2008
Vancouver 1996 “One World One Hope”
Vancouver 1996
“One World One Hope”
% Progression to AIDS in 3 yrs
Plasma Viral Load, a strong
Predictor of outcome in
CD4+
100 cells/µL
> 750
HIV Infected Individuals
80 501-750
351-500
60 201-350
< 200
40
High Plasma Viral Load: Poor Prognosis
20
Low Plasma Viral Load: Good Prognosis
0
> 30 10-30 3-10 0.5-3 < 0.5
Plasma HIV RNA (thousand copies/mL)
J Mellors et al. Annals 1997
Montaner et al JAMA, March 25th 1998
Vancouver 1996
“One World One Hope” AZT + NVP
AZT + ddI
% Progression to AIDS in 3 yrs
100
CD4+
cells/µL Triple Therapy: AZT + ddI + NVP
> 750
80 501-750
351-500
60 201-350
< 200 Gulick et al; JAMA, July 1, 1998
40
0
20
Change in Viral Load
0
> 30 10-30 3-10 0.5-3 < 0.5
-1
Plasma HIV RNA (thousand copies/mL) Dual Therapy Regimens
J Mellors et al. Annals 1997
-2
Triple Therapy: AZT+3TC+IDV
-3
0 52
Study Weeks
Impact of HAART in BC-CfE
140 Death Rate per 1000
120 Greater than 85% reduction
100
in death rate among those
80
engaged in care
60
40
20
0
1993-94 1995-96 1997-98 1999-00 2001-02 2003-04
Modified from Hogg et al, Lancet. 2009
Impact of HAART in BC-CfE
140 Death Rate per 1000 35 Life Expectancy at age 20
120 30
100 25
80 20
60 15
40 10
20 5
0 0
1993-94 1995-96 1997-98 1999-00 2001-02 2003-04 1993-94 1995-96 1997-98 1999-00 2001-02 2003-04
Modified from Hogg et al, Lancet. 2009
HAART Can Reduce HIV Transmission
HAART stops HIV replication
↓
HIV levels fall to undetectable in blood
as well as in sexual fluids
↓
Sharp reduction in HIV transmissionPrevention Strategies
- Education
- Change in behavoir
- Harm reduction
- New strategies/technology
- Vaccines
Existing strategies have failed
to contain the global HIV pandemicVertical Transmission Canada, 1990 to 2008 Modified from Alimenti et al CAHR, 2009
Discordant Couples
S Attia, M Egger, M Muller, M Zwahlen and N Lowa. AIDS. 2009 Jul 17;23(11):1397-404Discordant Couples
Studies of heterosexual discordant couples observed no
transmission in patients treated with ART and with viral load
below 400 c/ml, but data were compatible with one
transmission per 79 person-years.
S Attia, M Egger, M Muller, M Zwahlen and N Lowa. AIDS. 2009 Jul 17;23(11):1397-404B&M Gates Fdn: HIV Transmission Risk in
Heterosexual Serodiscordant Couples
3,400 couples In 7 African countries
All counseled and given free condoms
HAART initiated based on CD4 count eligibility
Over the next 1 to 3 years, 103 new HIV infections
All but 1 infection occurred in the untreated couples
Estimated 92% reduction of HIV transmission by HAART
Unadjusted relative risk: 0.17 (95% CI: 0.004-0.94; P = .037)
Adjusted relative risk: 0.08 (95% CI: 0.002-0.57; P = .004)
Adjusted for visit and CD4+ cell count at initiation
Donnell D, et al. CROI 2010. Abstract 136.B&M Gates Fdn: HIV Transmission Risk in
Heterosexual Serodiscordant Couples
3,400
Morecouples
recentlyInan7email
Africanhascountries
been circulated saying that:
All “counseled
The singleand case of transmission
given free condoms involved a man
who initiated ARVs 18 days before his 12-month
HAART
study initiated
visit. At this based
visit hisonpartner
CD4 count
testedeligibility
positive for HIV,
Over the next having
1 tobeen negative
3 years, at month
103 new 9.”
HIV infections
All but 1 infection occurred in the untreated couples
Estimated 92% reduction of HIV transmission by HAART
Unadjusted relative risk: 0.17 (95% CI: 0.004-0.94; P = .037)
Adjusted relative risk: 0.08 (95% CI: 0.002-0.57; P = .004)
Adjusted for visit and CD4+ cell count at initiation
Donnell D, et al. CROI 2010. Abstract 136.Wood et al, BMJ, 2009
Wood et al, BMJ, 2009 Whiskers represent 95% confidence intervals.
Wood et al, BMJ, 2009 Whiskers represent 95% confidence intervals.
Wood et al, BMJ, May 16, 2009
Impact of HAART in BC-CfE
Frequency of people
6 months Baseline
Plasma Viral Load (log10 copies/mL) Distribution
Modified from Anema et al. EIDJ 2009Impact of HAART in BC-CfE
Frequency of people
Baseline
24 months
Plasma Viral Load (log10 copies/mL) Distribution
Modified from Anema et al. EIDJ 2009New HIV and Syphilis in BC
Rate per 100,000 population
M REKART, BC-CDC, 2006New HIV and Syphilis in BC
Rate per 100,000 population
M REKART, BC-CDC, 2006Cost-Effectiveness of HAART
BC-DTP
“HIV deficit” in BC in 2005: 400
Cost of Medical Management of 1 HIV infection over a
lifetime = $250,000
800 cases per year
Averted lifetime Rx cost up to 2001 US $96.4M
A total of 3,963 pts were on HAART in BC in 2005 400 cases per year
Total actual drug cost (using patented drugs) in 2005
$49 million USCost-Effectiveness of HAART
BC-DTP
“HIV deficit” in BC in 2005: 400
Cost of Medical Management of 1 HIV infection over a
lifetime = $250,000
Averted lifetime Rx cost up to U$A 100M
A total of 3,963 pts were on HAART in BC in 2005
Total actual drug cost (using patented drugs) in 2005
U$A 50MThe Bc-CfE Mathematical Model
Viviane D. Lima et al
JID 2008Adhe re nc e : 0 % -
Incremental net benefit (Millions
of CDN $) over 30 years
Overall population and
patient-centered
Net Benefit (million $ Can 2005)
800
Overall Population
Patient-Centered incremental net benefit of
600
increasing uptake of
HAART from 50% to 75%
400
over 30 years, based on a
200
willingness-to-pay
thresholds of $50,000 per
0
0 5 10 15 20 25 30
quality-adjusted life year.
Time (years)
K Johnston et al, submitted, 2010Summary HAART is widely regarded as a cost effective, life- saving strategy ↓ Mortality of treated HIV/AIDS patients ↓ Morbidity of treated HIV/AIDS patients ↓ Health Resource utilization ↓ Vertical Transmission of HIV infection Furthermore, when the impact of HAART on HIV transmission is considered, HAART expansion becomes a cost-averting strategy
The third approach, though, is the most intriguing. This is to do nothing more than press ahead faster with the treatment program. Since treatment reduces viral load, it should, in theory, make those being treated less infectious. Of course, theory is one thing and practice another. But studies in Taiwan and British Columbia (the latter by Julio Montaner, the incoming president of the International AIDS Society, which organizes the conference) have shown big falls in transmission rates as ARVs have been rolled out.
The Power of HAART: Demographic Model
Treat 30%
HIV prevalence Cost of treatment
Treat all Treat 30%
Treat all
Number of
infections
prevented
Montaner et al, Lancet 2006R Granich, C Gilks, C Dye, K De Cock, B Williams. The Lancet Nov 26th 2008
AIDS Nov 27th 2008, The Economist
Deploying the drugs used to treat AIDS may be the way to limit its spread
Illustration by Peter Schrank
Thank youAIDS Nov 27th 2008, The Economist
Deploying the drugs used to treat AIDS may be the way to limit its spread
Illustration by Peter Schrank
Thank youAn Alternative Approach Preliminary Results
Methods
Prospective ecological study in BC, Canada
Used administrative records to evaluate the association
between expansion of HAART coverage, population level
plasma HIV-1-viral load and new HIV diagnoses
HIV testing, CD4 & viral load testing and HAART
distribution are centralized and free in BC
Data for second half of 2009 is preliminary due to delayed
reporting, therefore only the first half of 2009 was used for
statistical analyses
Montaner et al, CROI 2010January 2004
Summer of 1996
The second expansion of HAART
occurred prior to the new 2008
IAS-USA Guidelines, which were
adopted in BC at the end of 2008
The first expansion of HAART
occurred as a result of the new 1996
IAS-USA Guidelines, which were
adopted in BC in the summer of
1996
Year
Montaner et al, CROI 20101.00
Incidence/yr
0.20
0.10
0.04 Acquired resistance
1.00
falling
0.02
0.01
0.201995 2000 2005 2010
< 50/mL (%)
90
Viral load
0.10
80
Plasma viral load
0.04 suppression rising
70
0.02
0.01
60
1995 2000 2005 2010Number of Active HAART
Participants and Number of New
Number of Active HAART Participants
HIV+ Diagnoses per Year
Number of New HIV+ Diagnoses
p=0.015
New HIV+ Diagnoses (All)
Active on HAART
New HIV+ Diagnoses (IDU)
Year Montaner et al, CROI 2010Number of Active HAART
Participants and Number of New
Number of Active HAART Participants
HIV+ Diagnoses per Year
Number of New HIV+ Diagnoses
p=0.015
New HIV+ Diagnoses (All)
Active on HAART
p=0.085
New HIV+ Diagnoses (IDU)
p=0.026
Year Montaner et al, CROI 2010“True” New Yearly HIV Diagnoses in BC
BC-CDC Updated March 2010HIV testing in BC, 1985 to 2008
Year # of HIV Tests
Jan 2004
BC-CDC Report, 2009Hepatitis C, 1999-2008 Infectious Syphilis, 1999-2008
• BC 2004
• BC
2004
x Canada
x Canada
Genital Chlamydia, 1999-2008 Gonorrhea, 1999-2008
• BC x Canada
x Canada
2004 • BC 2004Highest
Non IDU HIV-1- Plasma
Viral load per
Year
IDU
Ever on Treatment
&
Censoring at the time of
Death or Move
The proportion of HIV infected IDUs engaged in care in BC with plasma viral
load >1500 c/mL, as a surrogate for “high” community HIV-1-viral load,
decreased from ~50% in 2000-04 to ~20% in 2009 (p“Provincial Viral Load”
All Patients Ever Tested for Plasma HIV-1-Viral Load in BC
Censoring at the time of Death or MoveNew Data: Pre HAART CD4 Count
Montaner et al, 2010, Preliminary DataCommunity pVL and New HIV Diagnoses
San Francisco
30,000 P = .005 for Mean CVL
Mean Community Viral Load (copies/mL)
association*
Number of Newly Diagnosed HIV Cases
1200
Newly diagnosed and
25,000 reported HIV cases
1000
20,000
800
798
15,000
600
642
10,000 523 518
434 400
5000 200
0 0
2004 2005 2006 2007 2008
*Data insufficient to prove significant association with reduced HIV incidence.
Das-Douglas M, et al. CROI 2010. Abstract 33.A Formidable Challenge A Unique Opportunity
When to Start HAART?
A matter of Perspective
Viral Load
CD4 Count
yearsWhen to Start HAART?
A matter of Perspective
Viral Load
CD4 Count
years
yearsWhen to Start HAART?
A matter of Perspective
Viral Load
CD4 Count
years
years
yearsWhen to Start HAART?
A matter of Perspective
Viral Load
CD4 Count
years
years
yearsPerson years on ART (M) Cost: 2010 to 2050
70 7
60 6
50 5
Deaths (M)
Cost (Bn$)
40 4
30 3
20 2
10 1
0 0
0
Current
1
200
2
350
3
500
4
Immediate
5 6
Economics of ART up to 2050 in South Africa
Current policy vs. Universal Access at different CD4 counts
Granich. CROI 2010STOP HIV & AIDS:
AIDS Seek and Treat to
Optimally Prevent HIV & AIDS*
* Supported through a $2.5M five year Avant Garde Award by the
National Institute for Drug Abuse (NIDA) at the NIH in 2008 and
$48M (+ drugs) four year outreach grant by BC Govt in 2010STOP HIV & AIDS:
AIDS Seek and Treat to
Optimally Prevent HIV & AIDS*
Prospectively Evaluate the Impact of HAART Expansion
on AIDS Morbidity and Mortality and HIV Incidence in BC
Intervention Primary Endpoint
HAART Expansion HIV Incidence
within medical guidelines at years 3 to 5
Secondary Endpoints:
MORBIDITY AND MORTALITY, CD4 COUNTS, HIV-1-RNA LEVELS,
RESISTANCE, ADVERSE EVENTS, SAFETY, ADHERENCE,
HOSPITALIZATIONS, RESOURCE UTILIZATION
* Supported through a $2.5M five year Avant Garde Award by the
National Institute for Drug Abuse (NIDA) at the NIH in 2008 and
$48M (+ drugs) four year outreach grant by BC Govt in 2010HAART Expansion to Reduce AIDS
Morbidity & Mortality, and HIV Incidence
HAART has a substantial added preventive value
The magnitude of this effect is not yet fully characterized, and
may well vary in different settings
Seek and Treat among those who have a medical indication for
HAART cannot wait for the above to be resolved
Many lives will be saved and much insight will be gained from
closely monitoring a more “aggressive”roll out of HAART within Rx
Guidelines
Seek and Treat outside the range where treatment is medically
indicated remains a research question
However, Rx Guidelines leave few outside the “treatment
envelope”
TAP should serve to re-energize Universal AccessCombination prevention
Biomedical
Interventions
HIV testing,
Structural linkage to care
Interventions and expanded
HAART
HIV coverage
Prevention
Individual
Community and small
Interventions group
behavioral
interventions
Modified from T. CoatesA Statistician’s Opinion
All scientific work is incomplete - whether it be
observational or experimental. All scientific work is
liable to be upset or modified by advancing
knowledge. That does not confer upon us a freedom
to ignore the knowledge we already have, or to
postpone the action that it appears to demand at a
given time.
Bradford-Hill, A. 1965 The environment and disease: Association or
Causation? President address at January 14 meeting. Proceedings of the
Royal Society of Medicine 163 (seriesB): 295-300Seek and Treat to Optimally
Prevent HIV & AIDS
STOP HIV & AIDS
R Hogg, E Wood, T Kerr, M Tyndall, A Levy, PR Harrigan,
Viviane Lima, Aranka Anema, Stephen Smith, Warren O’Brien
Pedro Cahn, Jose Esparza, Craig Mc Clure, Robin Gorna
Jacques Normand, Nora Volkow
IAS - USA ART Guidelines Panel, IAS, WHO and UNAIDS
BC-MoH and MHL&S
SPH Foundation
Merck, Gilead, ViiV
MSHRF, CIHR, NIDA and NIH
H&W, Ottawa
Research Staff and Study Participants
British Columbia
Centre for Excellence
in HIV/AIDSBritish Columbia Centre for Excellence in HIV/AIDS Thank You
You can also read
